Method and apparatus for treating bone fractures, and/or for fortifying and/or augmenting bone, including the provision and use of composite implants, and novel composite structures which may be used for medical and non-medical applications

ABSTRACT

A composite comprising: a barrier, said barrier being configured to selectively pass water, and said barrier being degradable in the presence of water; a matrix material for disposition within said barrier, wherein said matrix material has a flowable state and a set state, and wherein said matrix material is degradable in the presence of water; and at least one reinforcing element for disposition within said barrier and integration with said matrix material, wherein said at least one reinforcing element is degradable in the presence of water, and further wherein, upon the degradation of said at least one reinforcing element in the presence of water, provides an agent for modulating the degradation rate of said matrix material in the presence of water.

REFERENCE TO PENDING PRIOR PATENT APPLICATIONS

This patent application:

(1) is a continuation-in-part of pending prior International (PCT)Patent Application No. PCT/US14/71572, filed Dec. 19, 2014 by 206 ORTHO,Inc. for METHOD AND APPARATUS FOR TREATING BONE FRACTURES, AND/OR FORFORTIFYING AND/OR AUGMENTING BONE, INCLUDING THE PROVISION AND USE OFCOMPOSITE IMPLANTS, AND NOVEL COMPOSITE STRUCTURES WHICH MAY BE USED FORMEDICAL AND NON-MEDICAL APPLICATIONS (Attorney's Docket No. 206ORTHO-13PCT), which patent application:

-   -   (A) is a continuation-in-part of pending prior International        (PCT) Patent Application No. PCT/US14/39394, filed May 23, 2014        by 206 ORTHO, Inc. for METHOD AND APPARATUS FOR TREATING BONE        FRACTURES, AND/OR FOR FORTIFYING AND/OR AUGMENTING BONE,        INCLUDING THE PROVISION AND USE OF COMPOSITE IMPLANTS        (Attorney's Docket No. 206 ORTHO-040506 PCT), which patent        application:        -   (i) is a continuation-in-part of pending prior U.S. patent            application Ser. No. 13/781,473, filed Feb. 28, 2013 by            Jeffrey A. D'Agostino et al. for METHOD AND APPARATUS FOR            TREATING BONE FRACTURES, AND/OR FOR FORTIFYING AND/OR            AUGMENTING BONE, INCLUDING THE PROVISION AND USE OF            COMPOSITE IMPLANTS (Attorney's Docket No. 206 ORTHO-1),            which patent application:            -   (a) is a continuation-in-part of prior U.S. patent                application Ser. No. 13/452,273, filed Apr. 20, 2012 by                Jeffrey A. D'Agostino et al. for IMPLANTABLE POLYMER FOR                BONE AND VASCULAR LESIONS (Attorney's Docket No.                111137-0002), which patent application in turn (1) is a                continuation-in-part of prior International (PCT) Patent                Application No. PCT/US2011/057124, filed Oct. 20, 2011,                and (2) claims benefit of prior U.S. Provisional Patent                Application Ser. No. 61/394,968, filed Oct. 20, 2010;                and            -   (b) claims benefit of prior U.S. Provisional Patent                Application Ser. No. 61/604,632, filed Feb. 29, 2012 by                Jeffrey D'Agostino et al. for SPLINT INJECTION                (Attorney's Docket No. 0330.00005; 206 ORTHO-1 PROV);        -   (ii) claims benefit of prior U.S. Provisional Patent            Application Ser. No. 61/826,983, filed May 23, 2013 by            Jeffrey D'Agostino et al. for METHOD AND APPARATUS FOR            TREATING BONE FRACTURES, AND/OR FOR FORTIFYING AND/OR            AUGMENTING BONE, INCLUDING THE PROVISION AND USE OF            COMPOSITE IMPLANTS INCLUDING THERMOPLASTICS (Attorney's            Docket No. IP206ORTHOPROV010; 206 ORTHO-4 PROV);        -   (iii) claims benefit of prior U.S. Provisional Patent            Application Ser. No. 61/826,994, filed May 23, 2013 by            Jeffrey D'Agostino et al. for METHOD AND APPARATUS FOR            TREATING BONE FRACTURES, AND/OR FOR FORTIFYING AND/OR            AUGMENTING BONE, INCLUDING THE PROVISION AND USE OF            COMPOSITE IMPLANTS INCLUDING URETHANES (Attorney's Docket            No. IP206ORTHOPROV011; 206 ORTHO-5 PROV);        -   (iv) claims benefit of prior U.S. Provisional Patent            Application Ser. No. 61/828,463, filed May 29, 2013 by            Jeffrey A. D'Agostino et al. for METHOD AND APPARATUS FOR            TREATING BONE FRACTURES, AND/OR FOR FORTIFYING AND/OR            AUGMENTING BONE, INCLUDING THE PROVISION AND USE OF            COMPOSITE IMPLANTS (Attorney's Docket No. IP206ORTHOPROV012;            206 ORTHO-6 PROV); and        -   (v) claims benefit of prior U.S. Provisional Patent            Application Ser. No. 61/883,062, filed Sep. 26, 2013 by 206            ORTHO, Inc. and Jeffrey A. D'Agostino et al. for METHOD AND            APPARATUS FOR TREATING BONE FRACTURES, AND/OR FOR FORTIFYING            AND/OR AUGMENTING BONE, INCLUDING THE PROVISION AND USE OF            COMPOSITE IMPLANTS (Attorney's Docket No. 206 ORTHO-8 PROV);    -   (B) claims benefit of prior U.S. Provisional Patent Application        Ser. No. 61/918,088, filed Dec. 19, 2013 by 206 ORTHO, Inc. and        Robert S. Whitehouse et al. for BIORESORBABLE AND BIODEGRADEABLE        COMPOSITE MATERIALS (Attorney's Docket No. 206 ORTHO-13 PROV);        and    -   (C) claims benefit of prior U.S. Provisional Patent Application        Ser. No. 61/944,629, filed Feb. 26, 2014 by 206 ORTHO, Inc. and        Robert S. Whitehouse for NOVEL BALLOON FOR MEDICAL IMPLANTS        (Attorney's Docket No. 206 ORTHO-14 PROV);

(2) claims benefit of pending prior U.S. Provisional Patent ApplicationSer. No. 61/990,464, filed May 8, 2014 by 206 ORTHO, Inc. and Jeffrey A.D'Agostino et al. for METHODS AND COMPOSITIONS FOR PREDICTABLYCONTROLLING THE ONSET AND RATE OF MATERIAL DEGREDATION (Attorney'sDocket No. 206 ORTHO-20 PROV); and

(3) claims benefit of pending prior U.S. Provisional Patent ApplicationSer. No. 62/059,059, filed Oct. 2, 2014 by 206 ORTHO, Inc. and ArthurWatterson et al. for HIGH PERFORMANCE BIODEGRADABLE MATERIAL WITHTUNABLE DURATION PROPERTIES (Attorney's Docket No. 206 ORTHO-21 PROV).

The fifteen (15) above-identified patent applications are herebyincorporated herein by reference.

FIELD OF THE INVENTION

This invention relates to methods and apparatus for treating bones, andmore particularly to methods and apparatus for treating bone fracturesand/or for fortifying and/or augmenting bone in mammals, and relates tonovel composite structures which may be used for medical and non-medicalapplications.

BACKGROUND OF THE INVENTION

It is common for bones to become fractured as the result of a fall, anautomobile accident, a sporting injury, etc. In these circumstances, itis common to reinforce the bone in the area of the fracture so as tosupport the bone during healing.

To this end, current treatment options typically comprise externalstabilizers (e.g., plaster casts, braces, etc.) and internal stabilizers(e.g., screws, bone plates, intramedullary nails, etc.).

External stabilizers such as casts and external braces suffer from anumber of disadvantages. For one thing, they can interfere with apatient's normal daily activities, e.g., it can be difficult to wearclothing over a cast, or to operate a motor vehicle with a cast, etc.Furthermore, with animals, external casting and bracing of somefractures can be extremely difficult. In addition, with externalstabilizers, the soft tissue interposed between the bone and theexternal stabilizer is used to transmit load from the bone to theexternal stabilizer. As a result, shortly after application of theexternal stabilizer, the patient's intervening soft tissue will begin toatrophy through disuse, thereby requiring further rehabilitation for thepatient. Furthermore, as the intervening soft tissue atrophies, theclose supporting fit of the external stabilizer is disrupted and, as aresult, effective load transfer is undermined.

Internal stabilizers such as pins, screws, bone plates, intramedullarynails, etc. generally provide a more effective stabilization of thefracture, since they are able to directly interface with the bone.However, installing these internal stabilizers requires an invasivesurgical procedure, e.g., a relatively large incision, etc. Furthermore,after healing of the fracture, the internal stabilizers (screws, boneplates, intramedullary nails, etc.) should, ideally, be removed so as toallow the bone to fully recover its mechanical strength. This, however,requires a second surgical procedure, with additional trauma to thepatient.

In some circumstances (e.g., such as with fractures in vertebralbodies), bone cements may be injected into the interior of the bone inan attempt to stabilize the bone. However, such bone cements suffer fromdisadvantages of their own. More particularly, such bone cements aretypically ceramic cements, polymer-based cements (e.g., polymethylmethacrylate, also known as PMMA) or calcium salt-based cements. Whilethese bone cements are typically capable of withstanding significantcompressive loading, they are also extremely brittle and typicallycannot withstand significant tensile loading. This limits theirapplication in instances where the loading on the bone may include atensile component. This means that bone cements are not suitable for usein many situations, particularly in long bones (e.g., the tibia).Additionally, the failure mode for brittle materials results incatastrophic failure that includes the creation of shards of materialwhich are difficult to remove and create potential dangers for theanatomy.

The aforementioned polymers and cements can be molded into useful shapesor injected (i.e., applied in situ) which results in an anisotropicalignment of the polymer crystals, or they can be drawn and annealed byextrusion or pultrusion methods, which align the polymer crystals in anisotropic manner such that a favored directional mechanical advantagecan be established that is greater than the molded or injected method.This is the way some polymer pins are formed. There are drawbacks tothis practice and the materials used. There remains a top strength tothe final form that may not be appropriate for all bone-reinforcementactivities. There is a limit to the diameter of the final form that canbe aligned, since pultrusion and extrusion heat from the outside to aidin aligning the polymer crystals, and larger diameter devices will havea core of material which is not heated and therefore is not aligned.Finally, the isotropic alignment augments performance in one directionsuch as compression but may increase brittleness in side shear ortorsion.

Thus it will be seen that a new approach is needed for treating bonefractures.

In addition to the foregoing, in some circumstances a medical condition(e.g., osteoporosis) can weaken or damage a bone, including the creationof voids within the bone, and it may be desirable to fortify and/oraugment a bone so that it can better withstand the forces associatedwith normal physical activity. Unfortunately, however, theaforementioned external stabilizers, internal stabilizers and bonecements have all proven inadequate for fortifying and/or augmenting abone, e.g., for the reasons given above.

Thus it will be seen that a new approach is also needed for fortifyingand/or augmenting a bone.

The present invention also relates to novel composite structures whichmay be used for medical and non-medical applications.

SUMMARY OF THE INVENTION

The present invention provides a new approach for treating bonefractures.

The present invention also provides a new approach for fortifying and/oraugmenting a bone.

More particularly, the present invention comprises the provision and useof a novel composite implant for treating bone fractures and/or forfortifying and/or augmenting a bone. The composite implant is createdfrom at least one reinforcing element, embedded within a matrix. Thematrix material of the composite implant can be either anisotropic orisotropic, depending on the requirements of the final construct. Thecomposite implant is disposed within the intramedullary canal of a bone,or within another opening in the bone, either directly or within acontainment bag, so as to function as an internal “splint”, whereby tocarry the stress created during patient activity. This allows a bonefracture to heal, or provides fortification and/or augmentation of abone, with minimum inconvenience to the patient. The composite implantcomprises a plurality of components that are introduced sequentiallyinto the patient, and assembled in-situ, wherein each of the componentshas a size and flexibility which allows it to be installed using aminimally invasive approach while collectively providing the requiredstructural reinforcement for the bone which is being treated.Significantly, the properties of the composite implant can be customtailored for different treatment situations, e.g., the composite implantcan have different lengths and/or different cross-sectional dimensions,the composite implant can have different compressive and/or tensilestrengths, etc., all according to the individual needs of a particularpatient.

Composite implants have the added advantage of being tough, i.e.,non-brittle, such that the failure mode does not result in catastrophicshattering. The ductility of a composite implant, and the interlockingof reinforcing and/or fibrous elements contained within the implant, isresistant to complete separation, thus there may be an element thatbreaks down, however, the final composite implant will not fullysegment.

In one preferred form of the invention, the composite implant comprisesthree components: a containment bag, one or more reinforcing elementsand an injectable matrix material.

The containment bag serves to protect the remaining components of thecomposite implant from the ingress of blood and/or other bodily fluidsthat might interfere with the deployment of the one or more reinforcingelements and/or interfere with the deployment or solidification of theinjectable matrix material. The containment bag also serves to constrainthe flow of the injectable matrix material while the injectable matrixmaterial is in its injectable state. The containment bag is flexible andmay be fabricated from a resorbable polymer such as a polyurethane,polylactic acid, glycolic acid or some mixture/copolymer thereof.Alternatively, the containment bag may be formed from fibers that arewoven, braided, knit, nonwoven, and/or otherwise worked so as to form amesh bag. Suitable fibers include polylactic acid, polyglycolic acid,polydioxanone or mixtures/copolymers thereof. In any case, thecontainment bag preferably has sufficient strength to allow theinjectable matrix material to be injected into the containment bag undersubstantial pressure and/or vacuum so as to ensure good interfacialcontact between the injectable matrix material and the one or morereinforcing elements, and to minimize voids within the containment bag,and to ensure good interfacial contact between the composite implant andthe bone. Ideally the mesh bag is hydrophobic so as to minimize theingress of bodily fluids into the containment bag that may otherwiseinterfere with the deployment or solidification of the variouscomponents of the composite implant.

Alternatively, the mesh bag may have a limited porosity to allow someegress of the injectable matrix material out of the containment bag,e.g., to osseointegrate with the surrounding bone. The containment bagmay have a hydrophobicity and porosity that affects the biocompatibilityand degradation of the composite implant by modulating the ingress ofwater into the interior of the containment bag. Where the containmentbag is filled through a filling port, the filling port is preferablyconstructed so that it may be closed off, e.g., by incorporating aone-way valve in the filling port or by providing a closure mechanism(e.g., a cap). The containment bag also provides a way to control thedegradation rate of the composite implant, by modifying the diffusion ofwater, blood, or other bodily fluids into the composite implant. Suchingress of fluids can degrade the composite implant (and/or itscomponents) and reduce the mechanical properties of the compositeimplant at a faster (or slower) rate than may be desirable. Potentialapproaches for forming a water vapor barrier include ceramic coatings,metal coatings, and water-reactive coatings on the containment bag.Furthermore, the degradation of the composite implant (and/or itscomponents) can also be slowed (or accelerated) by the addition of highaspect ratio platelet-shaped additives, water-reactive compounds, and/orinorganic or organic buffering agents in the containment bag. Theseadditives, compounds and/or buffering agents can be mixed (as additives)into the formulation of the containment bag, or can be contained inprotective micro- or nano-capsules.

Also, one or more compliant containment bags can be used for eachcomposite implant. This approach can provide an improved barrier, andcan also serve as a “backup” in case the first containment bag leaks,e.g., due to tearing, scratching, or contact during a surgicalprocedure. Microspheres that contain “self-healing” (or “self-sealing”)polymerizable chemistries can also be added into the formulation of thecontainment bag in order to prevent leakage due to accidental scratchingand tearing.

The one or more reinforcing elements comprise (i) flexible reinforcingsheets (which are preferably in the form of flexible concentricreinforcing tubes or flexible rolled reinforcing sheets), with theflexible reinforcing sheets comprising filaments formed into a textile(i.e., woven, braided, knit, nonwoven, and/or otherwise worked so as toform the flexible reinforcing sheets) or incorporated into a film so asto form the flexible reinforcing sheets, (ii) flexible reinforcing rods,with the flexible reinforcing rods comprising a plurality of filamentswhich are held together by an outer sheath of a textile or film (whichmay or may not have the same composition as the aforementioned flexiblereinforcing sheets), or by a compacted (wound or compressed, etc.)connecting structure of a textile or film, or by a binder such as anadhesive, with or without surface projections for improved integrationwith the injectable matrix material, (iii) particulates (e.g.,particles, granules, segments, nanotubes, whiskers, nanorods, etc.), or(iv) combinations of the foregoing. Where the one or more reinforcingelements comprise flexible reinforcing sheets and/or flexiblereinforcing rods, the one or more reinforcing elements preferably havesufficient column strength to allow longitudinal delivery into thecontainment bag by pushing, and preferably have a configuration (e.g.,smooth outer surfaces, tapered ends, coatings, etc.) to facilitatemovement past other reinforcing elements and/or intervening structures(e.g., catheter structures). Furthermore, where the one or morereinforcing elements comprise flexible reinforcing sheets (e.g.,concentric tubes or rolled sheets) which are intended to be radiallycompressed during delivery to facilitate passage through a small opening(e.g., a catheter or surgical opening), the flexible reinforcing sheets(e.g., concentric tubes or rolled sheets) may comprise resilientelements (e.g., resilient rings) to assist their subsequent return to anexpanded state when positioned within the containment bag.

The filaments and particulates used to form the aforementionedreinforcing elements may be biodegradable or bioabsorbable, ornon-biodegradable or non-bioabsorbable. By way of example but notlimitation, suitable biodegradable or bioabsorbable materials includepolyglycolide (PGA), glycolide copolymers, glycolide/lactide copolymers(PGA/PLA), glycolide/trimethylene carbonate copolymers (PGA/TMC),stereoisomers and copolymers of polylactide, poly-L-lactide (PLLA),poly-D-lactide (PDLA), poly-DL-lactide (PDLLA), L-lactide, DL-lactidecopolymers, L-lactide, D-lactide copolymers, lactide tetramethyleneglycolide copolymers, lactide/trimethylene carbonate copolymers,lactide/delta-valerolactone copolymers, lactide/epsilon-caprolactonecopolymers, polydepsipeptide (glycine-DL-lactide copolymer),polylactide/ethylene oxide copolymers, asymmetrically 3,6-substitutedpoly-1,4-dioxane-2,4-diones, poly-β hydroxybutyrate (PHBA),PHBA/beta-hydroxyvalerate copolymers (PHBA/PHVA),poly-beta.-hydroxypropionate (PHPA), poly-beta-dioxanone (PDS),poly-DELTA-valerolactone, poly-DELTA-caprolactone, methylmethacrylate-N-vinyl pyrrolidone copolymers, citric acid polymers suchas polydiolcitrates, citric acid polyurethanes, urethane-doped citricacid-based polyesters, and poly (xylitol-co-citrate), polyester amides,oxalic acid polyesters, polydihydropyrans, polypeptides from alpha-aminoacids, poly-beta-maleic acid (PMLA), poly-beta-alkanoic acids,polyethylene oxide (PEO), silk, collagen, derivatized hyaluronic acidand chitin polymers, and resorbable metals, resorbable ceramics, andphosphate, borate, and silicate soluble glasses containing otherinorganic ions. By way of further example but not limitation, suitablenon-biodegradable or non-bioabsorbable materials include polyolefins,polyamides, polyesters and polyimides, polyetheretherketone (PEEK), andcarbon fiber, and metals, ceramics, and glasses.

As will hereinafter be discussed, the one or more reinforcing elementsare selected by the physician so as to provide the composite implantwith the desired size, stiffness and strength. Thus, and as willhereinafter be discussed, the physician may select from a variety ofdifferent reinforcing elements, each having a particular composition andlength, and preferably deliver those reinforcing elements sequentiallyto the patient, whereby to provide the composite implant with thedesired size, stiffness and strength. The physician may, optionally,size the reinforcement elements to the appropriate length.

The injectable matrix material is preferably polymeric and is preferablybiodegradable. The matrix material is preferably a multi-componentpolymer system that is mixed immediately prior to introduction into thepatient. Preferably, each of the components and the mixture haveviscosities less than 3000 cps. Optionally, the injectable matrixmaterial may contain a biocompatible solvent, with the solvent reducingviscosity so as to allow the matrix material to be injected, and withthe solvent thereafter rapidly diffusing from the composite implant soas to facilitate or provide stiffening of the composite implant. Thesolvent may also be used to alter the porosity of the injectable matrixmaterial.

In one preferred form of the invention, the injectable matrix materialis preferably an organic polymer that can be formed via a polymerizationprocess.

If desired, the injectable matrix material may also comprise a bioactiveor insoluble filler material, a therapeutic agent, and/or an agent toenhance visibility while imaging the composite implant.

In one preferred form of the invention, the injectable matrix materialcomprises a polymer comprising a blend of (i) one or more reactants witha least two functional groups, (ii) a low molecular weight functionalmodifier, and (iii) a poly functional aliphatic or cycloaliphaticisocyanate crosslinker. The matrix polymer may, optionally, also include(iv) a catalyst. The un-crosslinked blend has a glass transitiontemperature of between about 170° K to 250° K (i.e., −103.2° C. to−23.5° C.).

The first component (i.e., one or more reactants with at least twofunctional groups) preferably comprises (a) hydroxyl functional reactionproducts of a C2 to C16 aliphatic or cycloaliphatic or heterocyclicdiols or triols or tetrols or blends of these polyols with a saturatedor unsaturated C2 to C36 aliphatic dicarboxylic or tricarboxylic acid,anhydrides or lactones and/or lactides and/or glycolides and/orcarbonates or blends of these carboxylic acids, or (b) amine functionalaspartic acid ester, or (c) CH-active compounds, or blends of theforegoing.

Examples of some of the typical dicarboxylic acid and polyols toprepared polyester polyols useful in the present invention are shown inU.S. Patent Application Publication No. 2013/0171397 and in U.S. Pat.Nos. 2,951,823 and 2,902,462.

The second component (i.e., a low molecular weight functional modifier)preferably comprises an aliphatic or cycloaliphatic or heterocyclic diolwith C2 to C12 carbons.

The third component (i.e., a poly functional aliphatic or cycloaliphaticisocyanate crosslinker) preferably comprises an isocyanurate (trimer),iminooxadiazine dione (asymmetric trimer), biuret, allophanate oruretdione (dimer) derivative (with an average functionality of between2.0 to 4) of an C4 to C15 aliphatic or cycloaliphatic diisocyanate orlysine diisocyanate, or a C4 to C15 aliphatic or cycloaliphaticdiisocyanate or lysine diisocyanate. The crosslinked network has acrosslink density with an average molecular weight between crosslinks ofbetween 200 to 500.

The fourth (optional) component (i.e., a catalyst) is preferablyselected from the group of metals such as bismuth, potassium, aluminum,titanium, zirconium compounds or a t-amine, or organo-tin compounds.

The foregoing polymer blend is reactive at a temperature of between 5°C. to 150° C., or 10° C. to 70° C., or 10° C. to 50° C. to form a rigidpolymer matrix with a Tg (glass transition temperature) between 273.2° K(0° C.) and 423° K (150° C.), more preferably between 273° K (0° C.) and373° K (100° C.), and more preferably between 313° K (40° C.) and 343° K(70° C.), and more preferably greater than 303° K (30° C.) and isbiodegradable over a maximum 5 year period and preferably within a 3year period. The polymer may also be cross-linked using other commonenergy processes such as lasers, energy processes such as lasers, energybeams and ultraviolet light or other energy sources.

The molar ratio of the above matrix is 0.8 to 1.3 reactant functionalgroup to isocyanate functional group.

The cross-linked network is formed at a temperature of between 20° C. to60° C. within a time period of less than 24 hours.

Optionally, the matrix may also include a non-reactive polyesterplasticizer in the amount of 0-30% of the weight of the matrix. Theplasticizer for the matrix may consist of non-reactive aliphaticpolyesters such as shown in U.S. Pat. No. 5,047,054 among others.

Optionally, the matrix can contain other typical ingredients used incomposites, and other formulated products such as paints, inks,adhesives and sealants. These other ingredients may be pigment or fillerparticles, surfactants, defoamers, and other commonly known and usedadditives

The above glass transition temperature Tg of the reactant can beobtained by measurements or also by calculation using the William LandelFerry Equation (WLF) M. L. Williams, R. F. Landel and J. D. Ferry, J.Am. Chem. Soc. 77,3701 (1955). The websitehttp://www.wernerblank.com/equat/ViSCTEMP3.htm provides a simple methodto convert viscosity of an oligomeric polymer to the Tg.

The above aliphatic and cycloaliphatic isocyanates are show inhttp://www.wernerblank.com/polyur/chemistry/isocyanate/isocyanat_overview.htm.

Above aspartic acid ester reactants are described in U.S. Pat. Nos.7,754,782; 5,847,195; 5,126,170; 5,236,741; 5,243,012; 5,489,704;5,516,873; 5,580,945; 5,597,930; 5,623,045; 5,633,389; 5,821,326;5,852,203; 6,107,436; 6,183,870; and 6,355,829, among others.

The above CH active compounds are the malonic acid ester of above diolsor triols or an acetoacetic ester of the above diols or triols.

In one preferred form of the invention, there is provided a novelcomposite comprising (i) a barrier (which may be a containment bag orcoating) which is water permeable and which contains hydrolyzable sitesso that the barrier will break down over time when placed in an aqueousenvironment (e.g., water, the body, etc.); (ii) a flowable/settablematrix which is hydrolyzable so that the matrix will break down overtime when contacted by an aqueous environment; and (iii) reinforcingelements which are disposed within the flowable/settable matrix andwhich, when they come into contact with an aqueous environment, breakdown and give off catalysts which modify (e.g., increase) the hydrolysisof the matrix material. Thus, in this form of the invention, the barrierprovides a means for regulating the degradation of the matrix material,and the reinforcing elements provide a means for modifying (e.g.,increasing) the hydrolysis of the matrix material.

The composite implant is disposed within the intramedullary canal of abone, or within another opening in the bone, so as to function as aninternal “splint”, whereby to carry the stress created during patientactivity. This allows a bone fracture to heal, or provides fortificationand/or augmentation of bone, with minimum inconvenience to the patient.

As a modular system, each element of the composite implant is capable ofbeing delivered to a fracture site in a minimally invasive manner (e.g.,with an access point as small as 3 mm) and assembled within the body,i.e., with an in situ construction. This form of the invention isadvantageous, inasmuch as the final composite implant will have strengthcommensurate with the non-fractured bone and will be physically tough(i.e., non-brittle) but will have low impact on the patient's softtissue during implantation, thereby allowing a quicker return toactivities.

A containment bag can be used to protect the remaining components of thecomposite implant from the ingress of blood and/or other bodily fluidsthat might interfere with the deployment of the one or more reinforcingelements and/or interfere with the deployment or solidification of theinjectable matrix material.

In one preferred form of the invention, the components of the compositeimplant are introduced sequentially into the patient, and assembledin-situ, thereby allowing the composite implant to be installed using aminimally invasive approach.

In another preferred embodiment of the present invention, theaforementioned composite implant is preassembled for insertion via“open” procedures when minimally invasive procedures are not required orare not advantageous to the patient. In this situation, a pre-formedcomposite implant may be molded or pultruded so as to form a strongcomposite implant with features such as barbs, threads, and/or othermechanical features advantageous for implantation or to create blanksthat can be machined or over-molded to a final mechanical shape. If thecomposite implant is constructed using bioabsorbable materials, thecomposite nature of the composite implant will deliver superior strengthand toughness performance over products produced with a pure or blendedpolymer matrix. Additionally, the protrusion pultrusion or extrusionthat includes a reinforcement element will not have the restriction ondiameter imposed on polymer protrusion since alignment of the matrixpolymer crystals is of secondary import to the inclusion of thereinforcing element. The composite implant may be secured mechanically(threads) or by further use of injectable matrix material to fill thespaces and act as liquid threads for the composite implant.

In another preferred embodiment of the present invention, pre-cured pinsor rods can be fabricated and used to assemble the composite implant.These pre-cured pins or rods may be fabricated from the reinforcementelements and injectable matrix materials described elsewhere in thisapplication, and can be formed via processes such as extrusion,pultrusion, or molding. For example, reinforcement elements formed fromfiber braids can be preassembled as pre-cured rods for insertion via“open” procedures when minimally invasive procedures are not required orare not advantageous to the patient. Depending on the application, oneor more of such pre-cured rods or pins can be used in the procedure.Where pre-cured rods or pins are fabricated in this manner, thepre-cured rods or pins may be substantially rigid or they may have alimited degree of flexure. It is not required that the polymer matrix inthe pins or rods be fully cured; they can be cured after assembly.

Depending on the application, one or more of such pre-cured rods or pinscan be used in the procedure. In some applications, at least 3 or more,4 or more, or 5 or more rods can be used in a procedure, preferably withmaximum of 50 rods, or preferably a maximum of 40 rods, and morepreferably a maximum of 30 rods. In one preferred form of the invention,15-25 rods are used, which yields an excellent reinforcementelement-to-matrix material ratio (by volume) for optimal compositeimplant performance. The bending modulus of the rods can be between 2GPa to 80 GPa, preferably greater than 10 GPa, more preferably greaterthan 15 GPa, and more preferably greater than 20 GPa. It should be notedthat it is not required for all the rods or pins to have the samematerial, modulus or shape, and rods of different materials, shapes andmodulus can be chosen depending on the application or procedure. In someapplications or procedures, the rods or pins can be heated to improvetheir flexibility for easier insertion in the bone, or the containmentbag.

In some applications, the diameter of the rods is less than 5 mm, morepreferably less than 4 mm, more preferably less than 3 mm, and mostpreferably between 0.25 mm and 2.5 mm. It should be noted it is notrequired for all the rods or pins to have the same material, modulus,diameters or shape, and rods of different materials, shapes, diametersand modulus can be chosen depending on the application or procedure.

By way of example but not limitation, the composite implant may be usedin the following manner to treat a fracture in the tibia.

The first step is to create an access hole into the bone that is to betreated. When treating fractures in long bones, the hole is made intothe intramedullary canal distal to, or proximal to, the fracture site.

The second step is to remove or harvest the bone marrow (and/or othermatter) in the intramedullary canal, and to clean the intramedullarycanal, so as to provide a space for the composite implant. This is donethrough the access hole previously created. In one preferred form of theinvention, the device for removing or harvesting of the bone marrow fromthe intramedullary canal comprises a catheter with provision forintroducing a liquid or gas into the intramedullary canal and suctionfor removal of material from the intramedullary canal. The liquid or gascan be used to disrupt the content in the intramedullary canal orprepare the intramedullary canal for a composite implant. The liquid orgas can be introduced in a continuous, pulsed, or intermittent flow. Arotatable flexible rod, with a shaped end or attachment at the distalend, is optionally used to disrupt the bone marrow in the intramedullarycanal so as to aid in the removal of the bone marrow. When harvest ofthe bone marrow is required, a tissue trap is utilized.

The third step, if needed, is to place a flow restrictor plug in theintramedullary canal distal to, and/or proximal to, where the compositeimplant will be placed in the intramedullary canal. Again, this is donethrough the access hole previously created. The flow restrictor plugsmay be placed prior to the removal or harvest of the bone marrow (and/orother matter) to define the area to be cleaned. Where two flowrestrictor plugs are used, the two flow restrictor plugs may beconnected to one another.

The fourth step, if needed, is to return the bone to proper alignment.

The fifth step is to introduce the containment bag into theintramedullary canal via the access hole previously created. In onepreferred form of the invention, the containment bag is introduced intothe intramedullary canal through a delivery catheter, and is releasablyattached to a catheter that is used for subsequent delivery of theremaining components of the composite implant, i.e., the one or morereinforcement elements and the injectable matrix material. Note that theflexible (and compressible) nature of the containment bag facilitatesits delivery into the intramedullary canal via a minimally invasiveapproach (i.e., via the access hole previously created). The containmentbag may comprise an auxiliary channel to allow monitoring and control ofsubsequent pressure within the containment bag. The auxiliary channelmay be used to remove entrapped air from the composite implant duringfilling of the containment bag with the injectable matrix material. Theauxiliary channel may also be used to pressurize or depressurize (createa vacuum) the injectable matrix material so as to enhance bonding of theinjectable matrix material with adjacent structures (e.g., thereinforcing elements, the containment bag, bone, etc.). This auxiliarychannel may be parallel to the delivery catheter, or inside the deliverycatheter, or the auxiliary channel may be at the distal end of thecontainment bag. Alternatively, there may be a valve at the distal endof the containment bag, or at other strategic regions of the containmentbag, that can limit pressure within the containment bag.

The sixth step is to sequentially introduce the one or more reinforcingelements into the containment bag. This is done through the access holepreviously created. Note that the flexible nature of the reinforcingelements facilitates their delivery into the containment bag via theaccess hole previously created. Alternatively, the reinforcing elementsare reversibly made flexible via external energy, such as theapplication of heat or an electrical current, prior to insertion throughthe catheter, and attain maximum strength (or return to full strength)once delivered to the target area to be splinted. The one or morereinforcing structures are preferably introduced into the containmentbag sequentially so as to build up a reinforcing mass. In one preferredform of the invention, a plurality of flexible concentric reinforcingtubes are sequentially inserted into the containment bag, with oneflexible reinforcing tube being nested inside another, and a pluralityof flexible reinforcing rods are sequentially inserted within theinnermost concentric reinforcing tube. In one preferred form of theinvention, the flexible reinforcing sheets (which are preferably in theform of concentric tubes or rolled sheets) are delivered to the interiorof the containment bag by pushing them out of a delivery tube or,alternatively, by carrying them into the containment bag while heldwithin a delivery tube and then retracting the delivery tube, whereby toexpose the flexible reinforcing sheets. Preferably the size and numberof concentric reinforcing tubes and reinforcing rods are selected so asto meet the individual needs of a particular patient. The number ofconcentric reinforcing tubes utilized in the composite implant, and/ortheir lengths and/or cross-sectional dimensions, and/or the number ofreinforcing rods used, and/or their lengths and/or cross-sectionaldimensions, may be selected according to the individual needs of aparticular patient. Preferably the number, length, and cross-sectionaldimensions of the reinforcing tubes, and the number, length, andcross-sectional dimensions of the reinforcing rods, are selected so asto provide a composite implant having variable stiffness along itslength, e.g., a composite implant having a stiffer central region (e.g.,20 GPa) and less stiff distal and proximal ends (e.g., 3 GPa), wherebyto prevent stress risers from being created at the ends of the compositeimplant. To this end, the reinforcing tubes, and the reinforcing rods,are preferably provided in a variety of sizes with a range of mechanicalproperties for appropriate selection by the physician; alternatively,the reinforcing tubes and/or reinforcing rods may be sized at the timeof use by the physician. The reinforcing rods may include a polymermatrix, and the combination may be pre-cured to a rigid, or somewhatflexible, state so as to provide for the easier insertion of thereinforcing rods. If desired, a guidewire may be provided to facilitateintroduction of the one or more reinforcing elements into thecontainment bag. This guidewire is preferably attached to the distal endof the containment bag using an adhesive or other non-permanentattachment means. After the one or more reinforcement elements have beenplaced in the containment bag, the guidewire can be detached from thecontainment bag by pulling or twisting the guidewire. Alternatively, theguidewire may be absorbable, in which case it may be left in the patientat the conclusion of the procedure.

In one embodiment, one or more of reinforcing fibers, braids, pins, orrods are placed inside the containment bag before the containment bag isinserted into the bone canal, in which case the foregoing sixth step maynot be required.

The seventh step is to introduce the injectable matrix material into thecontainment bag. Again this is done through the access hole previouslycreated. In one preferred form of the invention, an injection tube isused to deliver the injectable matrix material into the containment bagunder pressure, where it flows over and through the one or morereinforcement structures contained within the containment bag. Vacuummay be used during the delivery of the injectable matrix material to aidin the wetting out of the reinforcement structures and removal oftrapped air. Vacuum may be achieved through a medical facility's common“wall” suction or through volume evacuation via a disposable syringe,such as a 60 cc syringe from Becton-Dickinson. The injection tube iswithdrawn after the matrix material is injected into the containmentbag. The injection tube is, preferably, also capable of transmitting anenergy wave (such as electro-magnetic, or electro-mechanical such asultrasonic vibration, light) into the injectable matrix material incases where pulsatile flow or the application of vibrational forces isrequired to aid injecting the matrix material into the containment bagor to initiate curing of the matrix material.

The eighth step is to solidify the injectable matrix material so thatthe matrix material, the one or more reinforcing elements and thecontainment bag become a single solidified structure capable ofproviding support across the fracture line while the bone fractureheals. This reaction can be catalyzed with energy(electromagnetic—alternating current or ultra-violet,acoustic—ultrasound, or electro-mechanical such as ultrasonicvibrations), a chemical catalyst with a time delayed action, or achemical catalyst released at a preferable time frame as per thedisruption of catalyst-filled micro-bubbles. Preferably, thesolidification process occurs at a rate that allows for complete fillingand wet-out of the composite structure prior to achieving a gel-likestate within minutes and hardens to a reasonably immovable mass withintens of minutes with a full hard state achieved within 5 days.

The ninth step is to close the wound.

Thus it will be seen that the present invention comprises the provisionand use of a novel composite implant for treating bone fractures (and/orfor fortifying and augmenting a bone). The composite implant is disposedwithin the intramedullary canal of the bone (or within another openingin the bone) so as to function as a “splint”, whereby to carry thestress created during patient activity. This approach allows the bonefracture to heal (or provides fortification and/or augmentation of abone) with minimum inconvenience to the patient. The composite implantcomprises a plurality of components that are introduced sequentiallyinto the patient, and assembled in situ, thereby allowing the compositeimplant to be installed using a minimally invasive approach.Significantly, the properties of the composite implant can be customtailored for different treatment situations, e.g., the composite implantcan have different lengths and/or cross-sectional dimensions, thecomposite implant can have different mechanical properties, e.g.compressive and/or tensile strengths, etc., all according to theindividual needs of a particular patient.

In another preferred form of the invention, the components of thecomposite implant are assembled or manufactured external to the body,and then introduced to the implant site, e.g., as an implant of variousgeometries such as pins, screws, or nails. In another form of theinvention, the injectable matrix material may partially pre-manufacturedexternal to the body, and further impregnated or interfaced with theimplant site by an additional amount of the injectable matrix materialhardened after the composite implant has been introduced to the implantsite in order to support the bone. For example, the reinforcement braidscan be combined with a polymer-based matrix and the combination ofbraids and matrix pre-cured so as to form pins or rods, and thesepre-cured pins or rods can then be introduced into the containment bagin the bone canal, followed by the injection of additional injectablematrix material to achieve the composite implant. Note that a singlebraid or fiber can be combined with matrix material so as to form thepins or rods; or multiple braids or fibers can be “glued together” withmatrix material so as to form the pins or rods. And note that a singlepin or rod can be placed inside the containment bag with matrixmaterial, whereby to form the composite implant; or multiple pins orrods can be placed inside the containment bag with matrix material,whereby to form the composite implant.

In another preferred form of the present invention, there is provided amethod for treating a bone, the method comprising:

selecting at least one reinforcing element to be combined with aninjectable matrix material so as to together form a composite implantcapable of supporting the bone;

positioning the at least one reinforcing element in a cavity in thebone;

flowing the injectable matrix material into the cavity in the bone sothat the injectable matrix material interfaces with the at least onereinforcing element; and

transforming the injectable matrix material from a flowable state to anon-flowable state so as to establish a static structure for thecomposite implant, such that the composite implant supports the adjacentbone.

In another preferred form of the present invention, there is provided acomposite implant comprising a containment bag, an injectable matrixmaterial for positioning within the containment bag, wherein theinjectable matrix material is flowable and settable, and at least onereinforcing element for positioning within the containment bag andintegration with the injectable matrix material, the at least onereinforcing element adding sufficient strength to the injectable matrixmaterial such that when the composite implant is disposed in a cavity ina bone, the composite implant supports the bone;

wherein the containment bag comprises a permeation barrier for providingat least one of (i) prohibiting or modulating the release of injectablematrix material out of the containment bag into the surroundingenvironment, and (ii) prohibiting or modulating the ingress of bodyfluids into the interior of the containment bag, whereby to regulatecontact of body fluids with the injectable matrix material and thereinforcing elements, whereby to regulate the degredation rate of theinjectable matrix material and the reinforcing elements.

In another preferred form of the present invention, there is provided amethod for treating a bone, the method comprising:

providing a containment bag, at least one reinforcing element to bepositioned within the containment bag, and an injectable matrix materialto be positioned within the containment bag so as to together form acomposite implant capable of supporting the bone, wherein thecontainment bag comprises a permeation barrier for providing at leastone of (i) prohibiting or modulating the release of injectable matrixmaterial out of the containment bag into the surrounding environment,and (ii) prohibiting or modulating the ingress of body fluids into theinterior of the containment bag, whereby to regulate contact of bodyfluids with the injectable matrix material and the reinforcing elements,whereby to regulate the degredation rate of the injectable matrixmaterial and the reinforcing elements;

positioning the containment bag in a cavity in the bone;

positioning the at least one reinforcing element in the containment bag;

flowing the injectable matrix material into the containment bag so thatthe injectable matrix material interfaces with the at least onereinforcing element; and

transforming the injectable matrix material from a flowable state to anon-flowable state so as to establish a static structure for thecomposite implant, such that the composite implant supports the adjacentbone.

In another preferred form of the present invention, there is provided athermoplastic polymer implant comprising a thermoplastic polymer matrixand a high modulus fiber component having a tensile modulus from about 8GPa to about 400 GPa.

In another preferred form of the present invention, there is provided amethod for treating a bone, the method comprising:

selecting at least one reinforcing element to be combined with aninjectable matrix material so as to together form a composite implantcapable of supporting the bone, wherein the at least one reinforcingelement comprises a high modulus fiber component having a tensilemodulus of about 8 GPa to about 400 GPa;

positioning the at least one reinforcing element in a cavity in thebone;

flowing the injectable matrix material into the cavity in the bone sothat the injectable matrix material interfaces with the at least onereinforcing element; and

transforming the injectable matrix material from a flowable state to anon-flowable state so as to establish a static structure for thecomposite implant, such that the composite implant supports the adjacentbone.

In another preferred form of the present invention, there is provided amethod for treating a bone, the method comprising:

selecting at least one high modulus fiber component having a tensilemodulus from about 8 GPa to about 400 GPa, wherein the at least one highmodulus fiber component comprises a rod having a cross-section selectedfrom the group consisting of round and circular;

flowing an injectable matrix material into the cavity in the bone sothat the injectable matrix material interfaces with the at least onehigh modulus fiber component so as to form a composite implant, whereinthe injectable matrix material comprises a thermoplastic polymer matrix;and

transforming the injectable matrix material from a flowable state to anon-flowable state so as to establish a static structure for thecomposite implant, such that the composite implant supports the adjacentbone.

In another preferred form of the present invention, there is provided amethod for treating a bone, the method comprising:

selecting at least one high modulus fiber component having a tensilemodulus from about 8 GPa to about 400 GPa, wherein the high modulusfiber component comprises a plurality of fibers, and further wherein thehigh modulus fiber component is pre-loaded with an injectable matrixmaterial just prior to implantation so as to together form a compositeimplant, wherein the injectable matrix material comprises athermoplastic polymer matrix;

positioning the composite implant in a cavity in the bone;

flowing additional injectable matrix material into the high modulusfiber component so that the injectable matrix material exudes from thesurfaces of the high modulus fiber component and interfaces with thesurrounding bone cavity; and

transforming the injectable matrix material from a flowable state to anon-flowable state so as to establish a static structure for thecomposite implant, such that the composite implant supports the adjacentbone and or approximated soft tissue.

In another preferred form of the present invention, there is provided apolymer implant comprising a high modulus fiber reinforcing componentand a urethane polymer matrix.

In another preferred form of the present invention, there is provided amethod for treating a bone, the method comprising:

selecting at least one high modulus fiber reinforcing component to becombined with a urethane polymer matrix so as to together form a polymerimplant capable of supporting the bone;

positioning the at least one high modulus fiber reinforcing component ina cavity in the bone;

flowing the urethane polymer matrix into the cavity in the bone so thatthe urethane polymer matrix interfaces with the at least one highmodulus fiber reinforcing component; and

transforming the urethane polymer matrix from a flowable state to anon-flowable state so as to establish a static structure for the polymerimplant, such that the polymer implant supports the adjacent bone.

In another preferred form of the present invention, there is provided amethod for treating a bone, the method comprising:

selecting at least one pre-formed polymer implant created from at leastone high modulus fiber reinforcing component combined with a urethanepolymer matrix so as to together form a polymer implant capable ofsupporting the bone;

positioning the at least one pre-formed polymer implant in a cavity inthe bone;

flowing a urethane polymer matrix into the cavity in the bone so thatthe urethane polymer matrix interfaces with the at least one pre-formedpolymer implant; and

transforming the urethane polymer matrix from a flowable state to anon-flowable state so as to establish a static structure for the polymerimplant, such that the polymer implant supports the adjacent bone.

In another preferred form of the present invention, there is provided amethod for treating a bone, the method comprising:

selecting at least one high modulus fiber reinforcing component which ispre-loaded with a urethane polymer matrix just prior to implantation soas to together form a polymer implant capable of supporting the boneonce fully cured;

positioning at least one high modulus fiber reinforcing component in acavity in the bone;

flowing additional urethane polymer matrix into the at least one highmodulus fiber reinforcing component so that the urethane polymer matrixexudes from the surfaces of the at least one high modulus fiberreinforcing component and interfaces with the surrounding bone cavity;and

transforming the urethane polymer matrix from a flowable state to anon-flowable state so as to establish a static structure for the polymerimplant, such that the polymer implant supports the adjacent bone and orapproximated soft tissue.

In another preferred form of the present invention, there is provided acomposite implant comprising an injectable matrix material which isflowable and settable, and at least one reinforcing element forintegration with the injectable matrix material, the injectable matrixmaterial comprising a resin, and the at least one reinforcing elementadding sufficient strength to the injectable matrix material such thatwhen the composite implant is disposed in a cavity in a bone, thecomposite implant supports the bone.

The present invention also relates to novel composite structures whichmay be used for medical and non-medical applications.

In another preferred form of the present invention, there is provided acomposite comprising:

a barrier, said barrier being configured to selectively pass water, andsaid barrier being degradable in the presence of water;

a matrix material for disposition within said barrier, wherein saidmatrix material has a flowable state and a set state, and wherein saidmatrix material is degradable in the presence of water; and

at least one reinforcing element for disposition within said barrier andintegration with said matrix material, wherein said at least onereinforcing element is degradable in the presence of water, and furtherwherein, upon the degradation of said at least one reinforcing elementin the presence of water, provides an agent for modulating thedegradation rate of said matrix material in the presence of water.

In another preferred form of the present invention, there is provided amethod for using a composite, said method comprising:

providing a composite comprising:

-   -   a barrier, said barrier being configured to selectively pass        water, and said barrier being degradable in the presence of        water;    -   a matrix material for disposition within said barrier, wherein        said matrix material has a flowable state and a set state, and        wherein said matrix material is degradable in the presence of        water; and    -   at least one reinforcing element for disposition within said        barrier and integration with said matrix material, wherein said        at least one reinforcing element is degradable in the presence        of water, and further wherein, upon the degradation of said at        least one reinforcing element in the presence of water, provides        an agent for modulating the degradation rate of said matrix        material in the presence of water; and

positioning said composite in an environment containing water.

In another preferred form of the present invention, there is provided amethod for treating a bone, said method comprising:

providing (i) a barrier, said barrier being configured to selectivelypass water, and said barrier being degradable in the presence of water;(ii) a matrix material, wherein said matrix material has a flowablestate and a set state, and wherein said matrix material is degradable inthe presence of water; and (iii) at least one reinforcing element whichis degradable in the presence of water, and further wherein, upon thedegradation of said at least one reinforcing element in the presence ofwater, provides an agent for modulating the degradation rate of saidmatrix material in the presence of water;

positioning said barrier in a cavity in the bone so as to create anenclosure;

positioning said at least one reinforcing element within said enclosure;

flowing said matrix material into said enclosure so that said matrixmaterial interfaces with said at least one reinforcing element; and

transforming said matrix material from a flowable state to a set stateso as to establish a static composite structure, such that said staticcomposite structure supports the adjacent bone.

BRIEF DESCRIPTION OF THE DRAWINGS

These and other objects and features of the present invention will bemore fully disclosed or rendered obvious by the following detaileddescription of the preferred embodiments of the invention, which is tobe considered together with the accompanying drawings wherein likenumbers refer to like parts, and further wherein:

FIGS. 1 and 2 are schematic views of a composite implant formed inaccordance with the present invention;

FIGS. 3 and 4 are schematic views of a concentric reinforcing tube thatmay be used to form the composite implant of FIGS. 1 and 2;

FIGS. 5 and 6 are schematic views of a rolled sheet that may be used toform the composite implant of FIGS. 1 and 2;

FIGS. 6A and 6B are schematic views showing how a flexible rolledreinforcing sheet may be radially compressed during delivery to thecontainment bag (FIG. 6A) and thereafter radially expanded (FIG. 6B)within the containment bag;

FIGS. 7 and 8 are schematic views of a flexible reinforcing rod that maybe used to form the composite implant of FIGS. 1 and 2;

FIGS. 8A, 8B, 8C and 8D are schematic views showing alternative forms ofthe flexible reinforcing rods of the present invention;

FIGS. 9-23 are schematic views showing a composite implant beingassembled in situ so as to treat a bone fracture;

FIGS. 24-26 show alternative forms of the composite implant of thepresent invention; and

FIG. 27 shows how the guidewire used to deliver the composite implantmay also be used to reduce a fracture and/or to help stabilize thefracture;

FIG. 28 is a graph showing material modulus vs. fiber volume;

FIG. 29 shows how the reinforcing elements may be formed from fiberscomprising columnar axial supports and angular cross fibers;

FIG. 30 shows the flexural modulus of various composite implants;

FIG. 31 shows the flexural modulus of other composite implants;

FIG. 32 shows the flexural modulus of still other composite implants;

FIG. 33 shows various composite implant configurations;

FIG. 34 shows other composite implant configurations;

FIG. 35 shows still other composite implant configurations;

FIG. 36 shows additional composite implant configurations;

FIG. 37 shows load versus position for various composite implants;

FIG. 38 shows flex modulus versus hours submerged for coated anduncoated containment bags;

FIG. 39 shows matrix fill volume versus time for different compositeimplant constructions;

FIG. 40 is a graph showing the flexural modulus of various glassreinforcing elements;

FIG. 41 is a graph showing the flexural modulus for variousconfigurations of reinforcing elements;

FIG. 42 is a graph showing composite pin weight loss versus starting pinglass content;

FIG. 43 is a graph showing pH versus time for various compositestructures;

FIG. 44 is a graph showing pH versus time for other compositestructures;

FIG. 45 is a schematic view showing a composite structure in the form ofa screw;

FIG. 46 is a schematic view showing a syringe formed out of a compositestructure; and

FIG. 47 is a schematic view showing a reinforcing element which may beused in the composite structure forming a syringe.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

The present invention provides a new approach for treating bonefractures using a composite implant.

The present invention also provides a new approach for fortifying and/oraugmenting a bone using a composite implant.

The present invention also relates to novel composite structures whichmay be used for medical and non-medical applications.

Composite Implant

More particularly, the present invention comprises the provision and useof a novel composite implant for treating bone fractures and/or forfortifying and/or augmenting a bone. The composite implant is disposedwithin the intramedullary canal of a bone, or within another opening inthe bone, so as to function as an internal “splint”, whereby to carrythe stress created during patient activity. This allows a bone fractureto heal, or provides fortification and/or augmentation of a bone, withminimum inconvenience to the patient. The composite implant comprises aplurality of components that are introduced sequentially into thepatient, and assembled in-situ, wherein each of the components has asize and flexibility that allows it to be installed using a minimallyinvasive approach while collectively providing the required structuralreinforcement for the bone that is being treated. Significantly, theproperties of the composite implant can be custom tailored for differenttreatment situations, e.g., the composite implant can have differentlengths and/or different cross-sectional dimensions, the compositeimplant can have different compressive and/or tensile strengths, etc.,all according to the individual needs of a particular patient. Alsosignificantly, the composite implant of the present invention isamenable to both in situ fabrication and pre-operative assembly of moreconventional means.

In one preferred form of the invention, and looking now at FIGS. 1 and2, the composite implant 5 comprises three components: a containment bag10, one or more reinforcing elements 15 and an injectable matrixmaterial 20.

Containment Bag

The containment bag 10 serves to protect the remaining components of thecomposite implant from the ingress of blood and/or other bodily fluidsthat might interfere with the deployment of the one or more reinforcingelements 15 and/or interfere with the deployment or solidification ofthe injectable matrix material 20. The containment bag 10 also serves toconstrain the flow of the injectable matrix material 20 while theinjectable matrix material 20 is in its injectable state. Therefore, thecontainment bag consists of a flexible enclosure (bag) and may include abiodegradable sealing mechanism such as a valve V (see FIGS. 12, 13, 20and 22).

The containment bag is flexible and may be fabricated from a resorbablepolymer such as a polyurethane, polylactic acid, glycolic acid or somemixture/copolymer thereof, or thermoplastics such as polycaprolactones(PCL), polylactic acids (PLA), polyhydroxybutyrates (PHB),polyhydroxyalkanoates (PHA),poly(3-hydroxybutyrate-co-3-hydroxyvalerates) (PHBV), citric acidpolymers such as polydiolcitrates, citric acid polyurethanes,urethane-doped citric acid-based polyesters, and poly(xylitol-co-citrate), and variations and blends and copolymers thereof,with variable crystallinity and/or molecular weight so as to adjust therate of the ingress of water or aqueous fluid through the bag. Thepolymers listed previously can also be compounded within a range of1-25% volume fraction, preferably 2-10% volume fraction, with nano-and/or micro-particulate with a range of sizes from 1 nm to 100 um, andmay, optionally, have a range of aspect ratios (either aligned ormisaligned), from 1-500 (length/diameter). The particulate can beinorganic materials such as bioabsorbable glasses, calcium phosphatesalts of any Ca/P ratio, carbon nano-structures, or nano-clays such ascloisite, halloysite, bentonite, or montmorillonite, or modifiednanoclays such as organomontmorillonite, or metal compounds includingcomposite oxides (such as magnesium oxide or magnesium hydroxide), etc.The particulate could also be organic, such as jute or silk fibers. Theparticulate can be used to improve mechanical properties of the bag.Particulate that is insoluble in a time frame relative to thesurrounding material and/or the composite within the barrier can act asa torturous path for water delaying ingress of aqueous media. Bothimproved mechanical properties and improved water barrier properties areparticularly effectively implemented when the aspect ratio is 10:1 orgreater, preferably 100:1 or greater, for two dimensions over a thirdsuch as with clays, iron oxide, aluminum oxide, silicon carbide, andmagnesium hydroxide (after certain heating schedules). The use ofparticulate is not limited to these uses. To effectively use theparticulates, dispersants and sizings/coatings may be required. Inparticular, a dispersant based on poly-hydroxy-stearic acid will bebiocompatible and assure proper spacing of the particulate within thepolymer layer. Similar sizings to those listed in the “sizings” sectionare also appropriate for aiding in bond strength and quality for theparticulates in the containment bag. Alternatively, the containment bag10 may be formed from fibers that are woven, braided, knit,electro-spun, nonwoven, and/or otherwise worked so as to form a meshbag. Suitable fibers include polylactic acid, polyglycolic acid,polydioxanone or mixtures/copolymers thereof, carbon fibers,bioresorbable and soluble glasses, and/or metal, and/or PHBs. Thecontainment bag can be formed by constructing sequential or alternatinglayers, typically between 1 and 25 layers, preferably between 2 and 7layers, of the same or varying materials in any combination, either byalternating axial orientation or not, such as by co-extrusion, heatpressing, or by any method of combining the materials. There is a “layermultiplication” technique that can build alternating nano-layers ofmaterial that decreases the water permeation tremendously. In addition,polymer layers with and without particulate can be sequentially builtusing methods such as solvent dip coating, dip casting, spray coating,and vapor deposition. The layers can be designed for different purposessuch as a high solvent (water) barrier layer (WVP—water vaporpermeability—between 10⁻² g*mm/m²*days and 10² g*mm/m²*days, preferablybetween 0.2 and 20 g*mm/m²*days, or more preferably between 0.3 and 15g*mm/m²*days, or more preferably between 0.2 and 8 g*mm/m²*days); ahighly compliant layer to aid with bag/balloon folding and toughness,and/or a layer for compatibalizing the balloon with the endosteum. Inany case, the containment bag preferably has sufficient strength toallow the injectable matrix material to be injected into the containmentbag under substantial pressure so as to ensure good interfacial contactbetween the injectable matrix material and the one or more reinforcingelements, the containment bag and the bone, and to minimize voids withinthe containment bag. The containment bag may be hydrophobic so as tominimize the ingress of bodily fluids into the containment bag that mayotherwise interfere with the deployment or solidification or acceleratethe degradation of the various components of the composite implant.Optionally, the containment bag may have a limited porosity to allowsome egress of the injectable matrix material 20 out of the containmentbag, e.g., to osseointegrate with the surrounding bone. In this respectit should be appreciated that such porosity may be varied across theextent of the containment bag so as to provide regions of greater orlesser porosity to the injectable matrix material 20, thus providingcontrol of the ability of the injectable matrix material to infiltratethe surrounding bone.

To control the diffusion rates into and out of the containment bag, thecontainment bag may be coated with a resorbable metal layer, such asmagnesium, silver, nickel, titanium, and/or metal alloys such asmagnesium calcium alloys. Such coatings can be applied via vaporcoating, sputtering, atomic layer deposition, chemical vapor deposition,or electroplating and electroless plating. Such metal layers providereduced diffusion, but can also react with water to providebasic/alkaline products that can act as buffering and degradationcontrol agents for the polymer matrix and/or glass fibers. Rather thanusing a coating, metal nano- or micro-particles can be added to theinjectable matrix material and/or the containment bag.

Another possible approach could be ceramic coatings on the containmentbag. Such coatings can be made by the surface reaction of ethyoxysilanessuch as tetraethoxysilane, methyltriethoxysilane,dimethyldiethoxysilane, or trimethylethoxysilane; polycarbosilane, orpolysilazanes such as perhydropolysilazane- or polysilizane-modifiedpolyamines.

The above coatings can be applied to the outside and/or inside surfacesof the containment bag, or can be included as an intermediate layer, forexample, magnesium- or magnesium alloy-based metal foil that issandwiched between other layers of the containment bag.

Significantly, the porosity of the containment bag may be set so as toregulate the permeability of body fluids into the interior of thecontainment bag, whereby to regulate contact of those body fluids withthe injectable matrix material and the reinforcing elements, whereby toregulate the degredation rate of the injectable matrix material and thereinforcing elements.

Thus, in one form of the invention, containment bag 10 comprises astructural barrier for constraining the disposition of one or morereinforcing elements 15 and injectable matrix material 20 within thebone. Significantly, containment bag 10 may comprise a permeationbarrier for prohibiting or modulating the release of injectable matrixmaterial 20 out of containment bag 10 and into the surroundingenvironment. Furthermore, containment bag 10 may comprise a permeationbarrier for prohibiting or modulating the ingress of body fluids intothe interior of the containment bag (and hence regulating thedegradation rate of injectable matrix material 20 and/or reinforcingelements 15 contained within the containment bag).

In one form of the invention, containment bag 10 comprises a PHA, e.g.,Polyhydroxybutyrate (PHB), poly-3-hydroxybutyrate (P3HB),poly-4-hydroxybutyrate (P4HB), polyhydroxyvalerate (PHV),polyhydroxyhexanoate (PHH), polyhydroxyoctanoate (PHO), 3HA acids, etc.

In one form of the invention, containment bag 10 comprises copolymersmade from made from monomers, e.g., glycolic acid, lactic acid,3-hydroxypropionic acid (3HP), 4-hydroxybutyrate (4HB),5-hydroxyvalerate (5HV), 3-hydroxyhexanoate (3HH), 6-hydroxyhexanoate(6HH), 3-hydroxyoctanoate (3HO), etc.

In one form of the invention, containment bag 10 comprises a PHAcopolymer, e.g., polyhydroxyoctanoate-co-hexanoate (PHOH),polyhydroxybutyrate-co-valerate (PHBV),3-polyhydroxybutytrate-co-4-polyhydroxybutyrate (PHBco4HB),3-polyhydroxybutytrate-co-5-polyhydroxy valerate,3-polyhydroxybutytrate-co-6-polyhydroxyhexanoate,poly-3-hydroxybutyrate-co-4-hydroxybutyrate copolymer, PHB4HB, PHBco4HB,PLA/P(3HB-3HH), etc.

Thus, in a further form of the invention, containment bag 10 comprises alayered structural barrier for constraining the disposition of one ormore reinforcing elements 15, optionally from 3 to 50 elements, or 4 to30 elements, or 5 to 25 elements, and injectable matrix material 20within the bone. Significantly, the inner layer of the containment bag10 may comprise a permeation barrier for prohibiting or modulating theingress of body fluids into the interior of the containment bag (andhence regulating the degradation rate of injectable matrix material 20and/or reinforcing elements 15 contained within the containment bag)using a bioabsorbable polymer such as, but not limited to, polylactic-acid with suspended insoluble particulate such as MagnesiumHydroxide with a plate-like morphology (WVP between 0.4 and 20g*mm/m²*days). A central layer of the containment bag may be constructedof an adhesive, relatively compliant bioabsorbable material such as poly(ε-capralactone) with or without suspended particulate that supplies atoughness and compliance to the bag structure. The final outer layercould be created using a bioabsorbable polymer with suspendedbio-compatibalizing agents, such as Hydroxy-apatite, such that theexternal layer of the balloon is compatibalized with the bone endosteum.

One or more such containment bags can be used for each compositeimplant. Where more than one containment bag is used for the compositeimplant, the multiple containment bags can provide an improved barrier,and/or can also serve as a “backup” in case the first containment bagleaks, due to tearing, scratching, or contact during a surgicalprocedure. Microspheres that contain “self-healing” (or “self-sealing”)polymerizable chemistries can also be added to the formulation of thecontainment bag to prevent leakage due to accidental scratching andtearing.

See Examples 84-95 for exemplary constructions forbiodegradable/absorbable barriers.

It should also be appreciated that containment bag 10 may be formed outof one or more of the materials used to form reinforcing elements 15and/or one or more of the materials used to form injectable matrixmaterial 20, appropriately processed so as to provide the functionalrequirements of containment bag 10.

Where the containment bag is filled through a filling port, the fillingport is preferably constructed so that it may be closed off, e.g., byincorporating a one-way valve (e.g., the valve V shown in FIGS. 12, 13,20 and 22) in the filling port or by providing a closure mechanism(e.g., a cap).

In some embodiments of the invention a sealing mechanism is required tocontain and seal the resin injection entry site while the compositesolidifies. In some forms of the invention, the sealing mechanism is amechanical valve (e.g., the valve V shown in FIGS. 12, 13, 20 and 22)and further is constructed of bioabsorbable polymers including some orall of those listed for the containment bag previously. The valve canhave one or more seal mechanisms such as overlapping, hinged plates, ornormally closed living hinges made of a compliant material. In otherforms of the invention, the sealing mechanism can be a rapidly curingreactive polymer system with or without a high barrier to water entry. Acombination of a mechanical system with a polymeric system can also beenvisioned.

In some embodiments of the sealing mechanism, the mechanism hasstructural features that allow it to be releasably connected to acatheter or other delivery device. This separable valve connection(e.g., the valve V shown in FIGS. 12, 13, 20 and 22) allows for the bagto be delivered to an intramedullary space, sequentially filled with thecomposite components, then sealed upon separation and removal of thedirecting catheter.

Thus a preferred form of the sealing mechanism envisions a structureconsisting of a series of two “duck-bill” valves separated by an openspace of between 1 mm and 50 mm axially or greater. The structure has aseparable connection to a catheter through and within which compositecomponents are deliverable. Upon completion of delivery of the uncuredresin components, the valves close due to applied vacuum, a normallyclosed design, or positive pressure from the resin with a portion of theresin filling the space between the two valves. The catheter is thenseparated from the bag, which remains in situ.

Reinforcing Elements

The one or more reinforcing elements 15 comprise (i) flexiblereinforcing sheets 22 (which are preferably in the form of concentrictubes such as is shown in FIGS. 3 and 4 or rolled sheets such as isshown in FIGS. 5 and 6), with the flexible reinforcing sheets 22comprising filaments 23 formed into a textile (i.e., woven, braided,knit, nonwoven, and/or otherwise worked so as to form the flexiblereinforcing sheets 22) or incorporated into a film so as to form theflexible reinforcing sheets 22, (ii) flexible reinforcing rods 35 (FIGS.7, 8, 8A, 8B, 8C and 8D), with the flexible reinforcing rods 35comprising a plurality of filaments 40 which are held together by anouter sheath 45 (FIGS. 7 and 8) of a textile or film (which may or maynot have the same composition and fiber orientation as theaforementioned flexible reinforcing sheets 22), or by a compacted (woundor compressed, etc.) connecting structure of a textile or film 45A(FIGS. 8A and 8B), or by a binder 46 (FIG. 8C) such as an adhesive, withor without surface projections 47 for improved integration withinjectable matrix material 20, (iii) particulates (e.g., particles,granules, segments, whiskers, nanotubes, nanorods, etc.), or (iv)combinations of the foregoing. Where the one or more reinforcingelements comprise flexible reinforcing sheets and/or flexiblereinforcing rods, the one or more reinforcing elements preferably havesufficient column strength to allow longitudinal delivery into thecontainment bag by pushing, and preferably have a configuration (e.g.,textured outer surfaces, tapered ends, etc.) to facilitate movement pastother reinforcing elements and/or intervening structures (e.g., catheterstructures). The one or more reinforcing elements preferably can beintroduced by means of a delivery catheter or sheath. Furthermore, wherethe one or more reinforcing elements comprise flexible reinforcingsheets (e.g., concentric tubes or rolled sheets) which are intended tobe radially compressed during delivery to facilitate passage through asmall opening (e.g., a catheter or surgical opening), the flexiblereinforcing sheets (e.g., concentric tubes or rolled sheets) maycomprise resilient elements 46 (e.g., resilient rings) to assist theirsubsequent return to an expanded state when positioned within thecontainment bag. The resilient elements may be thermosensitive or have ashape memory.

Thus, the composite implant of the present invention is formed fromreinforcing elements that may be made up of fibers from variousmaterials or “rods” of homogeneous or heterogeneous elements, configuredin a solid, wound, braided, woven, or interlink-stacked manner. The rodsmay or may not be likewise interwoven by further braiding, weaving, orwinding elements of similar or different fibrous elements.

The filaments, fibers, and particulates used to form the aforementionedreinforcing elements may be biodegradable or bioabsorbable, ornon-biodegradable or non-bioabsorbable. By way of example but notlimitation, suitable biodegradable or bioabsorbable materials includepolyglycolide (PGA), glycolide copolymers, glycolide/lactide copolymers(PGA/PLA), glycolide/trimethylene carbonate copolymers (PGA/TMC),stereoisomers and copolymers of polylactide, poly-L-lactide (PLLA),poly-D-lactide (PDLA), poly-DL-lactide (PDLLA), L-lactide, DL-lactidecopolymers, L-lactide, D-lactide copolymers, lactide tetramethyleneglycolide copolymers, lactide/trimethylene carbonate copolymers,lactide/delta-valerolactone copolymers, lactide/epsilon-caprolactonecopolymers, polydepsipeptide (glycine-DL-lactide copolymer),polylactide/ethylene oxide copolymers, asymmetrically 3,6-substitutedpoly-1,4-dioxane-2,4-diones, polyhydroxyalkanoates (PHA),poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV), poly-βhydroxybutyrate (PHB), poly-4-hydroxybutyrate (P4HB),PHB/beta-hydroxyvalerate copolymers (PHB/PHV),poly-beta.-hydroxypropionate (PHP), poly-beta-dioxanone (PDS),polyhydroxyhexanoate (PHH), polyhydroxyoctanoate (PHO),poly-DELTA-valerolactone, poly-DELTA-caprolactone, methylmethacrylate-N-vinyl pyrrolidone copolymers, polyester amides, oxalicacid polyesters, citric acid polyesters, polydihydropyrans, polypeptidesfrom alpha-amino acids, poly-beta-maleic acid (PMLA), poly-beta-alkanoicacids, polyethylene oxide (PEO), silk, collagen, derivatized hyaluronicacid and chitin polymers, and resorbable metals, resorbable metalalloys, resorbable ceramics, and phosphate, borate, and silicate solubleglasses containing other inorganic ions such as Fe, Ca, Sr, Zn, B, Mg,K, Mn, Ce, etc. By way of further example but not limitation, suitablenon-biodegradable or non-bioabsorbable materials include polyolefins,polyamides, polyesters and polyimides, polyetheretherketone (PEEK),polyetherketoneketone (PEKK), glass, ceramic, metal, silk, metal-cladfiber, and carbon fiber.

As will hereinafter be discussed, the one or more reinforcing elements15 are selected by the physician so as to provide the composite implantwith the desired size and mechanical properties, e.g. stiffness andstrength. Thus, and as will hereinafter be discussed, the physician mayselect from a variety of different reinforcing elements, each having aparticular composition and length, and preferably deliver thosereinforcing elements sequentially to the patient, whereby to provide thecomposite implant with the desired size and attributes of stiffness andstrength.

In one preferred form of the invention, the one or more reinforcingelements 15 comprise from about 5% to 85% (by volume) of the compositeimplant, typically at least 20% (by volume) of the composite implant.

In another embodiment, the reinforcing properties of the one or morereinforcing elements 15 may be modified by changing the materials,dimensions, shape, and surface characteristics of the fibers, filaments,and particulates.

In another embodiment, the reinforcing properties of the one or morereinforcing elements 15 may be modified by changing the orientation,volume, twist, and angle of the fibers and filaments within thereinforcing elements. In preferred constructions, the fibers andfilaments are typically set at an acute angle to intersecting fibers andfilaments in order to strengthen the reinforcing structure, but theangle may be any angle between 0 degrees and 90 degrees.

In another embodiment, the properties of the composite implant may bemodified by changing the orientation of one or more of the reinforcingelements 15, and/or by changing the volume of one or more of thereinforcing elements 15.

It will be appreciated that the properties of the composite implant maybe modified by changing the layup or selection of one or more of thereinforcing elements 15.

It will also be appreciated that the reinforcing properties, anddegradation profiles, of the one or more reinforcing elements 15 may bemodified by changing the material, dimensions, shape, orientation,volume, and surface features of the fibers, filaments, and/orparticulates used to form the one or more reinforcing elements 15.

Where the reinforcement elements comprise a textile, its reinforcingproperties and degradation profile may be modified by changing thematerials, orientation, length, shape, volume, twist, and angle of thefibers and filaments within the textile of the reinforcing elements. Thefibers and filaments in a textile of a reinforcing element arepreferably set at an acute angle to intersecting fibers and filaments,but the angle may vary between 0 degrees and 90 degrees or random.

It will be appreciated that the properties of the composite implant maybe modified by changing the layup or selection of one or more of thereinforcing elements.

It will also be appreciated that the reinforcing properties, and thedegradation profiles, of the one or more reinforcing elements may bemodified by changing the material, dimensions, shape, orientation,volume, and/or surface features of the fibers, filaments, and/orparticulates used to form the one or more reinforcing elements.

The shape of the reinforcement elements is generally important. Fortextiles, interwoven or braided materials can be formed as space fillersand skeletons for the composite implant. The shapes can be tailored forthe intended use, for example, triangular- or ribbon-shaped. Atriangular braided rod can be used as the reinforcement backbone of acomposite implant. The triangular shape (i.e., triangular cross-section)gives advantages over cylindrical shapes (i.e., cylindricalcross-section) in that the triangular shape is more applicable to atriangular intramedullary canal, additionally, each flat providing aplane of contact to spread impact force rather than a point load asoccurs with a circular configuration. Additionally, the nesting of flatagainst flat sides of the triangular shape provides a large surface areafor inter-rod binding by the resin. The triangular shape allows fornumerous configurations such as horizontal inter-locking of greater thantwo triangular rods resulting in a flat rod-like trapezoidal compositeimplant shape. This shape provides manufacturing flexibility, inasmuchas a single back-bone braid could be configured into multiple finalproducts. The triangular shape allows for very tight groupings ofmaterials that allow for very high fiber volumes not possible withcircular braids or other reinforcement materials which will always tendto have larger gaps between parallel axial reinforcement elements.

It should be noted that the use of multiple axially-orientedreinforcement elements made from textiles can be interlocked, eitherwith a surrounding binding fiber or with interwoven fiber elements, soas to increase resistance to catastrophic breakdown. Many currentnon-metallic implants fail due to catastrophic shear and compressivefracturing. The use of interlocked textiles in sheets or intrawovenaxial reinforcements can ensure failure occurs in a non-catastrophicyield rather than shear fracture mode as with metal implants. This isadvantageous as an orthopedic repair element. Additionally, it is knownthat composite materials can be superior to metals in response tochronic dynamic loading, i.e., resisting fatigue.

The reinforcing fibers or braids can also be pre-cured with polymermatrix to form pins or rods, which can then be used for the compositeimplant. Forming pre-cured pins or rods can facilitate their handlingand can prevent or retard degradation of the glass fiber in moisture.

Sizing.

The high modulus fiber may have a surface coated with a sizing agent orprimer that provides additional adhesion between an acrylic resininjectable matrix material and the high modulus fiber, and canoptionally act as a secondary catalyst for the polymerization of theacrylic monomers. In addition, the high modulus fiber may be surfacecoated with an amino functional material selected from at least one ofthe following materials: amino silanes, lysine, polyamines, amino acidsand polyamino acids.

The reinforcement fibers can be cleaned or surface oxidized usingvarious means described in the literature including plasma treatment,corona treatment, ozone treatment, and acidic/basic treatment. Suchtreatments can also be used to introduce specific chemical moieties,such as hydroxyl groups, on the surface of the fibers that can thatreact or provide improved adhesion with the polymer matrix.

Compatibility among the specific components that comprise a compositestructure is essential in order to ensure optimal interfacial bonding,mechanical properties, physical properties, and osseointegration.Compounds known as coupling agents or compatibilizers, which may beincorporated into the components of the composite implant, serve toenhance the chemical bonding between the specific components of thecomposite implant. In a preferred embodiment, the interfacial bondstrength between the containment bag, reinforcing elements, injectablematrix material, and bone can be enhanced through the addition of avariety of compatibilizers, e.g., calcium phosphate, hydroxyapatite,calcium apatite, fused-silica, aluminum oxide, apatite-wollastoniteglass, bioglass, compounds of calcium salt, phosphorus, sodium salt andsilicates, maleic anhydride, diisocyanate, epoxides, silane, andcellulose esters. These agents may be incorporated into, and/or appliedto, the components of the composite implant through a number of methods,e.g., plasma deposition, chemical vapor deposition, dip coating,melt-blending, spin or spray-on. A specific example is the applicationof a silane coupling agent to glass fiber reinforcement in order toincrease its interfacial bonding strength with the injectable matrixmaterial. Another example is the vapor deposition of calcium phosphateonto the inner surface of the containment bag such that the bondingbetween the injectable matrix material and the containment bag isenhanced. In order to increase the compatibility between the containmentbag and bone that it is supporting, dip-coating the exterior of thecontainment bag with an osseoconductive material (such as fused-silicawith aluminum oxide) will improve their adhesion to each other andaccelerate osseointegration.

The fibers may be sized with a resorbable metal layer, such asmagnesium, silver, nickel, titanium or metal alloys such as magnesiumcalcium alloys. Such coatings can be applied via vapor coating,sputtering, atomic layer deposition, chemical vapor deposition, orelectroplating and electroless plating. Another possible coating can beceramic coatings on the fibers. Such coatings can be made by the surfacereaction of ethyoxysilanes such as tetraethoxysilane,methyltriethoxysilane, dimethyldiethoxysilane, or trimethylethoxysilane;polycarbosilane, or polysilazanes such as perhydropolysilazane orpolysilizane modified polyamines.

Another possible approach for sizing utilizes inorganic salts such asmetal phosphates. This approach for sizing is similar to thepretreatment process of metals, wherein acids are used to corrode themetal and thus form metal salt on the surface which delays any furtherattack. Typically phosphate salts of iron, calcium, magnesium, zinc andnickel, etc. are used. The sizing can be applied to phosphate glassfibers by immersion in a suitable metal-salt solution which yields inertphosphate salts that are insoluble in water. This process isself-limiting, as the reaction takes place only as long as phosphateions are released from the glass surface. The reaction can take place ina reactive medium such as an alcohol or glycol. Mixture of salts ispreferred due the formation of smaller crystal sizes. This process couldalso be combined with an organic pretreatment. This combination ofsalt/organic pretreatment could also act as an adhesion promoter. Afterreaction, the glass fibers can be rinsed and/or vacuum dried. Multipleiteration can be performed with the same compound or different salts. Itis also possible to use only a metal phosphate, and diffuse some metalions into the glass fiber and obtain a metal clad fiber.

Those skilled in the art will recognize still other ways to modify theproperties of the composite implant in view of the present disclosure.

It should also be appreciated that reinforcing elements 15 may be formedout of one or more of the materials used to form containment bag 10and/or one or more of the materials used to form injectable matrixmaterial 20, appropriately processed so as to provide the functionalrequirements of reinforcing elements 15.

Injectable Matrix Material

The injectable matrix material 20 is preferably polymeric and ispreferably biodegradable. The injectable matrix material 20 is designedto be polymerized in situ but may be pre-formed prior to theapplication. The matrix material is preferably a multi-component polymersystem that is mixed immediately prior to introduction into the patient.Optionally, the injectable matrix material 20 may contain abiocompatible solvent, with the solvent reducing viscosity so as toallow the matrix material to be injected, and with the solventthereafter rapidly diffusing from the composite implant so as tofacilitate or provide stiffening of the composite implant 5. The solventmay also be used to alter the porosity of the injectable matrix material20.

In a preferred embodiment of the present invention, polyurethanes areutilized as the injectable matrix material, although other suitablechemistry systems will be apparent to those skilled in the art. Thepolyurethanes are produced through the reaction of a difunctional ormultifunctional isocyanate with a difunctional or multifunctionalcompound containing an active hydrogen, including water, hydroxylmaterials and amines. The urethane polymer matrix may comprise at leasttwo individual components that are mixed together to initiate the curingreaction, wherein a first component contains isocyanate functionalitiesand a second component contains active hydrogen functionalities capableof reacting with the isocyanate functionalities so as to form at leastone from the group consisting of urethane, urea, biuret and allophonategroups during the crosslinking reaction.

The first component may be selected from the group consisting of adiisocyanate molecule, a triisocyanate molecule, a polyisocyanatemolecule having at least two isocyanate groups per molecule, anisocyanate capped polyol having at least two free isocyanate groups permolecule, an isocyanate capped polyether polyol having at least two freeisocyanate groups per molecule and an isocyanate capped polyester polyolhaving at least two free isocyanate groups per molecule. Suitableisocyanates useful in the practice of this invention include, but arenot limited to, aromatic diisocyanates such as 1,2 and 1,4 toluenediisocyanate and blends, 2,4-toluene diisocyanate, 2,6-toluenediisocyanate, 2,2′-diphenylmethane diisocyanate, 2,4′-diphenylmethanediisocyanate, 4,4′-diphenylmethane diisocyanate, diphenyldimethylmethanediisocyanate, dibenzyl diisocyanate, naphthylene diisocyanate, phenylenediisocyanate, xylylene diisocyanate, methylene diphenyl diisocyanate(MDI) and polymeric MDI having an isocyanate functionality from about2.2 to about 2.8 isocyanate groups per molecule,4,4′-oxybis(phenylisocyanate) or tetramethylxylylene diisocyanate;aliphatic diisocyanates such as tetramethylene diisocyanate,hexamethylene diisocyanate, dimethyl diisocyanate, lysine diisocyanate,methyl lysine diisocyanate, lysine triisocyanate,2-methylpentane-1,5-diisocyanate, 3-methylpentane-1,5-diisocyanate or2,2,4-trimethylhexamethylene diisocyanate; and alicyclic diisocyanatessuch as isophorone diisocyanate, cyclohexane diisocyanate, hydrogenatedxylylene diisocyanate, hydrogenated diphenylmethane diisocyanate,hydrogenated trimethylxylylene diisocyanate, 2,4,6-trimethyl1,3-phenylene diisocyanate.

Or the first component may be a polyol isocyanate having a weightaverage molecular weight from about 200 to about 10,000.

Or the first component may be a blend of diisocyanate or triisocyanatemolecules with a polyol capped isocyanate having two, three or fourisocyanate groups per molecule in a ratio of about 1:99 percent byweight to about 99:1 percent by weight of the total isocyanate componentand has a viscosity at 25 degrees C. from about 250 cps to about 5,000cps.

The present invention comprises the use of these same multi-functionalisocyanates with multifunctional amines or multifunctional substitutedamines, multifunctional ketimines, multifunctional aldimines,isocyanurates or biurets. By way of example but not limitation, suchmultifunctional amines may include hexamethylene diamine, isophoronediamine, and lysine. Also trifunctional isocyanates such as lysinetriisocyanates. Examples of substituted amines may include N-substituteddiaspartic acid derivatives. Examples of multifunctional ketimines andaldimines may be made from the multifunctional amines mentionedpreviously and methyl isobutyl ketone or isobutyraldehyde.

The second component may be produced by the reaction product of adiamine, triamine or tetramine component with an activated vinylcomponent selected from the group consisting of dialkyl maleate, dialkylfumarate, an acrylic acid ester and vinyl ester, wherein the reactionratio is from about one equivalent of amine functionality to about oneequivalent of vinyl functionality to about four equivalents of aminefunctionality to about one equivalent of vinyl functionality.

Or the second component may be a blend of a polyol component and anaspartate molecule having from about 1% to about 99% polyol componentand from about 99% to about 1% aspartate, wherein at least one of thepolyol component and the aspartate molecule has a functionality towardsisocyanate of at least 2.1 active hydrogen groups per diisocyanatemolecule and a viscosity from about 250 cps to about 5000 cps at 25degrees C.

Or the second component may be selected from the group consisting of apolyol having at least two hydroxyl groups and up to four hydroxylgroups per molecule where the hydroxyl groups are primary or secondaryhydroxyls, a polyether polyol having at least two hydroxyl groups and upto four hydroxyl groups per molecule, a polyester polyol having at leasttwo hydroxyl groups and up to four hydroxyl groups per molecule wherethe polyester is formed by the reaction of a diol or trio with a diacid,a polyester polyol having at least two hydroxyl groups and up to fourhydroxyl groups per molecule where the polyester is formed by thereaction of hydroxyacid which is then endcapped with a diol or triol, anaspartate molecule, an amine molecule having from at least two aminegroups to four amine groups per molecule where the amine groups are aprimary or secondary amines, alkoxylated amines having at least twoterminal amine groups per molecule, and a compound containing at leasttwo of the following: aliphatic primary hydroxyl, aliphatic secondaryhydroxyl, primary amine, secondary amine and carboxylic acid groupswithin the one molecule.

Or the polyester polyol is selected from a reaction mixture primarily ofadipic acid with diethylene glycol, ethylene glycol or butane diol.

Or the second component can comprise a biodegradable crosslinker withhydroxyl functionality such as3-hydroxy-N,N-bis(2-hydroxyethyl)butanamide, or a blend of polyols alongwith the biodegradable crosslinker.

When a non-biodegradable implant is desired, the aromatic isocyanatesare generally favored. When a biodegradable implant is desired, thealiphatic isocyanates are generally favored. In an embodiment of thisinvention, the aliphatic isocyanates are preferred.

In a preferred embodiment of this invention, the isocyanate component isreacted with a polyol to produce a polyurethane. Suitable polyolsinclude, but not limited to, diols and triols of polycaprolactone,poly(caprolactone-co-lactide) andpoly(caprolactone-co-lactide-co-glycolide). Suitable dihydroxy compoundswhich may be utilized in the practice of this invention include, but arenot limited to, ethylene glycol, propylene glycol, butylene glycol,hexylene glycol and polyols including polyalkylene oxides, polyvinylalcohols, and the like. In some embodiments, the polyol compounds can bea polyalkylene oxide such as polyethylene oxide (“PEO”), polypropyleneoxide (“PPO”), block or random copolymers of polyethylene oxide (PEO)and polypropylene oxide (PPO). Higher functional polyol compounds arealso useful and can include glycerin, 1,2,4-butanetriol, trimethylolpropane, pentaerythritol and dipentaerythritol,1,1,4,4-tetrakis(hydroxymethyl)cyclohexane. Also polyols such as sugarsor starch. Other useful polyols can include triethanol amine andN,N,N′,N′-Tetrakis(2-hydroxyethyl)ethylenediamine.

The polyol materials discussed above may be used alone or, optionally,as mixtures thereof. The foregoing materials are merely examples ofuseful components for producing polyurethanes and should not be viewedas a limitation of the present invention. These higher functional polyolmaterials will produce highly crosslinked polyurethanes with highhardness and stiffness.

In preferred embodiments, the multifunctional hydroxyl material mayinclude at least one bioabsorbable group to alter the degradationprofile of the resulting branched, functionalized compound.Bioabsorbable groups which may be combined with the multifunctionalcompound include, but are not limited to, groups derived from glycolide,glycolic acid, lactide, lactic acid, caprolactone, dioxanone,trimethylene carbonate, 3-hydroxypropionic acid (3HP), 4-hydroxybutyrate(4HB), 5-hydroxyvalerate (5HV), 3-hydroxyhexanoate (3HH),6-hydroxyhexanoate (6HH), 3-hydroxyoctanoate (3HO), and combinationsthereof. For example, in one embodiment, the multifunctional compoundmay include trimethylol propane in combination with dioxanone andglycolide. Methods for adding bioabsorbable groups to a multifunctionalcompound are known in the art. Where the multifunctional compound ismodified to include bioabsorbable groups, the bioabsorbable groups maybe present in an amount ranging from about 50 percent to about 95percent of the combined weight of the multifunctional compound andbioabsorbable groups, typically from about 7 percent to about 90 percentof the combined weight of the multifunctional compound and bioabsorbablegroups.

The multifunctional compound can have a weight (average molecularweight) ranging from about 50 to about 50000, typically from about 100to about 30000, and preferably between about 150 to about 5000, andtypically possesses a functionality ranging from about 2 to about 6.

In a preferred embodiment, the polycaprolactone diols and triols providepolyurethanes that are biodegradable.

The isocyanate is reacted with a polyol to produce a prepolymer. Methodsfor endcapping the polyol with an isocyanate are known to those skilledin the art. For example, a polycaprolactone diol may be combined withisophorone diisocyanate by heating to a suitable temperature rangingfrom about 55 degrees C. to about 80 degrees C., typically about 70degrees C. The resulting diisocyanate-functional compound may then bestored until combined with additional polyol to form the finalpolyurethane product.

Reaction of the urethane prepolymer with polyol to form the finalpolyurethane product generally requires a catalyst to provide convenientworking and cure times. Polyurethane catalysts can be classified intotwo broad categories, amine compounds and organometallic complexes. Theycan be further classified as to their specificity, balance, and relativepower or efficiency. Traditional amine catalysts have been tertiaryamines such as triethylenediamine (TEDA, also known as1,4-diazabicyclo[2.2.2]octane or DABCO, an Air Products's trademark),dimethylcyclohexylamine (DMCHA), and dimethylethanolamine (DMEA).Tertiary amine catalysts are selected based on whether they drive theurethane (polyol+isocyanate, or gel) reaction, the urea(water+isocyanate, or blow) reaction, or the isocyanate trimerizationreaction (e.g., using potassium acetate, to form isocyanurate ringstructure). Since most tertiary amine catalysts will drive all threereactions to some extent, they are also selected based on how much theyfavor one reaction over another.

Another useful class of polyurethane catalysts are the organometalliccompounds based on mercury, lead, tin (dibutyl tin dilaurate), bismuth(bismuth octanoate), titanium complexes, zirconium complexes, zinccomplexes (imidazole complexed zinc), and iron complexes. Dibutyl tindilaurate is a widely used catalyst in many polyurethane formulations.Stannous octoate is another catalyst that may be used.

Another useful catalyst is 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU).

In the practice of this invention dibutyl tin dilaurate is a favoredcatalyst at concentrations below 0.5% and more preferably atconcentrations below 0.2% by weight.

The urethane polymer matrix may be crosslinked.

The crosslinked urethane polymer matrix may be configured to startdegrading in the body within about 1 month to about 36 months afterimplantation in the body.

The crosslinked urethane polymer matrix may be configured to lose atleast 50% of its original mechanical strength after 6 months in thebody.

The crosslinked urethane polymer matrix may be configured to lose atleast 80% of its original mechanical strength after 12 months in thebody.

In a preferred embodiment of this invention, the composite implant iscreated via the injection of a matrix material, preferably polymeric,through and around the reinforcing elements that may be a series ofbraided fibers, axial rods, bundled rods, bundled braided rods or othersuch configurations that conform to previous descriptions. The maximumcompressive and flexural modulus of the composite implant is that of thetheoretical compressive and flexural modulus of a composite implantformed completely out of reinforcing elements, the minimum compressiveand flexural modulus of the composite implant is that of the theoreticalcompressive and flexural modulus of a composite implant formedcompletely out of injectable matrix material. The final compressive andflexural modulus of the composite material is directly related to thepercent composition of fiber volume and will lie between the two values.Additionally, in one embodiment, the reinforcing elements may be braidedinto geometric formations which further increase or decrease themechanical properties of the composite implant. As an example, acomposite implant with all axial reinforcement elements will havehighest resistance to tension and compression, while a composite implantwith braided reinforcement elements with no axial reinforcement, butbiased reinforcement at approximately 45° to the axis of the compositeimplant, would be strong in flexural modulus but not as strong incompression. As another example, woven sheets of materials used asreinforcement elements may be designed with differing weaveconfigurations to achieve similar ends.

It should also be appreciated that injectable matrix material 20 may beformed out of one or more of the materials used to form containment bag10 and/or one or more of the materials used to form reinforcing elements15, appropriately processed so as to provide the functional requirementsof injectable matrix material 20.

In one preferred form of the invention, the injectable matrix materialcomprises a polymer comprising a blend of (i) one or more reactants witha least two functional groups 20 to 95% by weight, (ii) a low molecularweight functional modifier 0.1 to 30% by weight, and (iii) a polyfunctional aliphatic or cycloaliphatic isocyanate crosslinker in astoichiometric ratio with reactants from 0.8 to 1.3. The matrix polymermay, optionally, also include (iv) a catalyst. The un-crosslinked blendhas a glass transition temperature of between of about 170° K to 250° K(i.e., −103.2° C. to −23.5° C.).

The first component (i.e., one or more reactants with a least twofunctional groups) preferably comprises (a) hydroxyl functional reactionproducts of a C2 to C16 aliphatic or cycloaliphatic or heterocyclicdiols or triols or blends of these polyols with a saturated orunsaturated C2 to C36 aliphatic dicarboxylic or tricarboxylic acid,anhydrides or lactones and/or lactides and/or glycolides and/orcarbonates or blends of these carboxylic acids, or (b) amine functionalaspartic acid ester, or (c) CH-active compounds, or blends of theforegoing.

Examples of some of the typical dicarboxylic acid and polyols toprepared polyester polyols useful in the present invention are shown inU.S. Patent Application Publication No. 2013/0171397 and in U.S. Pat.Nos. 2,951,823 and 2,902,462.

The second component (i.e., a low molecular weight functional modifier)preferably comprises an aliphatic or cycloaliphatic or heterocyclic diolwith C2 to C12 carbons.

The third component (i.e., a poly functional aliphatic or cycloaliphaticisocyanate crosslinker) preferably comprises an isocyanurate (trimer),iminooxadiazine dione (asymmetric trimer), biuret, allophanate oruretdione (dimer) derivative (with an average functionality of between2.0 to 4) of an C4 to C15 aliphatic or cycloaliphatic diisocyanate orlysine diisocyanate, or a C4 to C15 aliphatic or cycloaliphaticdiisocyanate or lysine diisocyanate. The crosslinked network has acrosslink density with an average molecular weight between crosslinks ofbetween 200 to 500.

The fourth (optional) component (i.e., a catalyst) is preferablyselected from the group of metals such as bismuth, potassium, aluminum,titanium, zirconium compounds or a t-amine, or organo-tin compounds.

The foregoing polymer blend is reactive at a temperature of between 5°C. and 150° C., or 10° C. to 70° C., or 10° C. to 50° C. to form a rigidpolymer matrix with a Tg (glass transition temperature) between 273.2° K(0° C.) and 423° K (150° C.), more preferably between 273° K (0° C.) and373° K (100° C.), and more preferably between 313° K (40° C.) and 343° K(70° C.), and more preferably greater than 303° K (30° C.), and isbiodegradable over a maximum 5 year period and more preferably within a3 year period.

The molar ratio of the above matrix is 0.8 to 1.3 reactant functionalgroup to isocyanate functional group.

The crosslinked network is formed at a temperature of between 20° C. to60° C. within a time period of less than 24 hours.

Optionally, the matrix may also include a non-reactive polyesterplasticizer in the amount of 0-30% of the weight of the matrix. Theplasticizer for the matrix may consist of non-reactive aliphaticpolyesters as shown in U.S. Pat. No. 5,047,054 among others.

The above glass transition temperature Tg of the reactant can beobtained by measurements or also by calculation using the William LandelFerry Equation (WLF) M. L. Williams, R. F. Landel and J. D. Ferry, J.Am. Chem. Soc. 77,3701 (1955). The websitehttp://www.wernerblank.com/equat/ViSCTEMP3.htm provides a simple methodto convert viscosity Tg of an oligomeric polymer to the Tg.

The above aliphatic and cycloaliphatic isocyanates are show inhttp://www.wernerblank.com/polyur/chemistry/isocyanate/isocyanat_overview.htm.

Above aspartic acid ester reactants are described in U.S. Pat. Nos.7,754,782; 5,847,195; 5,126,170; 5,236,741; 5,243,012; 5,489,704;5,516,873; 5,580,945; 5,597,930; 5,623,045; 5,633,389; 5,821,326;5,852,203; 6,107,436; 6,183,870; and 6,355,829, among others.

The above CH active compounds are the malonic acid ester of above diolsor triols or an acetoacetic ester of the above diols or triols.

Additions to Injectable Matrix Material

If desired, the injectable matrix material 20 may also comprise abioactive or insoluble filler material, a therapeutic agent, and/or anagent to enhance visibility while imaging the composite implant.

Fillers.

The injectable matrix material may include a filler in the form ofbiocompatible, insoluble and/or osteoconductive particles or shortfibers. The first or primary filler, preferably in the form ofparticles, may also provide porosity, bone ingrowth surfaces andenhanced permeability or pore connectivity or resistivity to waterpermeation. One suitable particulate filler material is tricalciumphosphate, although other suitable filler materials will be apparent tothose skilled in the art such as orthophosphates, monocalciumphosphates, dicalcium phosphates, tricalcium phosphates, tetracalciumphosphates, amorphous calcium phosphates and combinations thereof. Alsobiodegradable/bioresorbable glasses can be utilized as a filler.

The filler particles may comprise a degradable polymer such aspolylactic acid, polyglycolic acid, polycaprolactone, hydroxybutyrate,hydroxypropionic acid, hydroxyhexanoate, and co-polymers thereof. Theparticles may also comprise degradable polymer containing one or moreinorganic fillers.

In one embodiment the inorganic filler particles have mean diametersranging from about 1 micron to about 20 microns and lengths of 1 micronto 500 microns. The inorganic filler particles can have differentshapes, including spherical, platelet-shaped, isotropic or anisotropic,fibers including nanofibers, rods, nanotubes, and nanorods.

In another embodiment the porosity and compressive properties of thematrix material may be modified by using additional fillers that may beinorganic, organic or another suitable biocompatible material. Suchrefinements include the addition of particles having mean diametersranging from about 10 microns to about 500 microns or a mean diameter ofless than 1 micron. In certain matrix materials the additional fillermaterials may be provided in one or more size distributions.

The composite implant can become porous after implantation so as to aidthe resorption and bone healing process. This porosity can be generatedby various mechanisms including the preferential resorption of filler,such as calcium sulfate or α-tricalcium phosphate, bioglass or of apolymeric component. Alternatively, the formulation can include abiocompatible solvent such as DMSO that is leached out of the implantpost implantation. The pores are preferably 100 μm in diameter withinterconnectivity to allow bone ingrowth.

The composite implant may also include an additional porogen. In oneform of the invention, the porogen is sugar or a polysaccharide, such asdextran, but other biocompatible porogens will be apparent to thoseskilled in the art such as crystalline materials in the form of solublesalts.

In another embodiment of the present invention, the filler, eitherinorganic or polymeric, may be present in combined amount ranging fromabout 10 to about 50 wt % of the matrix composition. In certain cases itmay be desirable to have the filler content over 50 wt %. If a porogenis added, it will preferably be present in an amount ranging from about15 to about 50 wt %.

Therapeutics Agents.

The inclusion of a therapeutic agent in the injectable matrix material,or in one or more of the reinforcing elements, is contemplated in thepractice of this invention. Therapeutic agents can include agents thatpromote bone formation, or for relief of pain. Agents may include, butare not limited to, parathyroid hormone, vitamin D, calcitonin, calcium,PO4, non-steroidal anti-inflammatory drugs (NSAIDS) such as, but notlimited to, acetaminophen, salicylates (aspirin, diflunisal, salsalate),acetic acid derivatives (indomethacin, ketorolac, sulindac etodolac,diclofenac, nabumetone), propionic acid derivatives (ibuprofen,naproxen, flurbiprofen, ketoprofen, oxaprozin, fenoprofen, loxoprofen),fenamic acid derivatives (meclofenamic acid, mefenamic acid, flufenamicacid, tolfenamic acid), oxicam (enolic acid) derivatives (piroxicam,meloxicam, tenoxicam, droxicam, lornoxicam, isoxicam), arylalkanoic acidderivatives (tolmetin); selective COX-2 inhibitors (celecoxib,rofecoxib, valdecoxib, parecoxib, lumiracoxib, etoricoxib, firocoxib);steroids such as, but not limited to, corticosteroids (hydrocortisone,hydrocortisone acetate, cortisone acetate, tixocortol pivalate,prednisolone, methylprednisolone, prednisone, triamcinolone acetonide,triamcinolone alcohol, mometasone, amcinonide, budesonide, desonide,fluocinonide, fluocinolone acetonide, halcinonide, betamethasone,dexamethasone, fluocortolone, hydrocortisone-17-valerate, aclometasonedipropionate, betamethasone valerate, betamethasone dipropionate,prednicarbate, clobetasone-17-butyrate, clobetasol-17-propionate,fluocortolone caproate, fluocortolone pivalate, or fluprednideneacetate); immune selective anti-inflammatory derivatives (ImSAIDs) suchas, but not limited to, submandibular gland peptide T (SGp-T) andderivatives phenylalanine-glutamine-glycine (FEG) and its D-isomericform (feG); narcotic compositions such as, but not limited to,buprenorphine, butorphanol, codeine, hydrocodone, hydromorphone,levorphail, meperidine, methadone, morphine, nalbuphine, oxycodone,oxymorphone, pentaxocine, or propoxyphene; other analgesic compositionssuch as, but not limited to, tramadol, or capsaicin; local anethetics(including short term acting anesthetics) such as, but not limited to,benzocaine, dibucaine, lidocaine, or prilocaine; bisphosphonates, orcombinations of any of the above.

Therapeutic agents delivered locally can use a carrier vehicle toprovide a protective environment, provide target delivery to cells orwithin cells, provide locally delivery, timed delivery, staged deliveryand/or use delivery technology know in the art.

The therapeutic agents can also include bone growth activating factors,such as bone morphogenetic proteins (BMPs), FGF (fibroblast growthfactor), VEGF (vascular endothelial growth factor), PDGF (plateletderived growth factor), or PGE2 (prostaglandin E2). Bone morphogeneticproteins can include BMP1, BMP2, BMP3, BMP4, BMP5, BMP6, BMP7, BMP8a,BMP8b, BMP10, or BMP15.

The therapeutic agents can also include inorganic material processed bythe body as a vitamin such as Fe, Ca, P, Zn, B, Mg, K, Mn, Ce, Sr. Theseelements are built into a predictably solubilizing component of thecomposite tuned for a consistent release.

Agent to Enhance Visibility.

It is also possible for the injectable matrix material to include one ormore particles or liquid agents to enhance visibility while imaging thecomposite implant. By way of example but not limitation, where thephysician may be using fluoroscopy to view the bone being treated andthe composite implant, the injectable matrix material may includebismuth oxychloride, bismuth subcarbonate, barium, barium sulfate,ethiodol, tantalum, titanium dioxide, tantalumpentoxide, tungsten,strontium carbonate, strontium halides platinum, titanium, silver, gold,palladium, iridium, osmium, copper, niobium, molybdenum, strontium,strontium salts and gallium, iodine substituted compounds/polymers,and/or alloys such as nickel-titanium, nickel-manganese-gallium,platinum-iridium, platinum-osmium to enhance the visibility of theinjectable matrix material under fluoroscopy.

Features of the Composite Implant

In a preferred embodiment of the invention, the composite implant iscreated via the introduction of the injectable matrix material,preferably polymeric, through and around the reinforcing elements, whichmay comprise a plurality of braided fibers, axial rods, bundled rods,bundled braided rods or other such configurations. The matrix materialand reinforcing elements may be surrounded by a barrier which may beused to regulate the rate at which water contacts the matrix materialand reinforcing elements.

In one preferred form of the invention, there is provided a novelcomposite comprising (i) a barrier (which may be a containment bag orcoating) which is water permeable and which contains hydrolyzable sitesso that the barrier will break down over time when placed in an aqueousenvironment (e.g., water, the body, etc.); (ii) a flowable/settablematrix which is hydrolyzable so that the matrix will break down overtime when contacted by an aqueous environment; and (iii) reinforcingelements which are disposed within the flowable/settable matrix andwhich, when they come into contact with an aqueous environment, breakdown and give off catalysts which modify (e.g., increase) the hydrolysisof the matrix material. Thus, in this form of the invention, the barrierprovides a means for regulating the degradation of the matrix material,and the reinforcing elements provide a means for modifying (e.g.,increasing) the hydrolysis of the matrix material.

The maximum compressive and flexural modulus of the composite implant isthat of the theoretical compressive and flexural modulus of a compositeimplant formed completely out of reinforcing elements, and the minimumcompressive and flexural modulus of the composite implant is that of thetheoretical compressive and flexural modulus of a composite implantformed completely out of injectable matrix material.

The final compressive and flexural modulus of the composite implant isdirectly related to the percent composition of fiber volume in thecomposite implant, i.e., a composite implant comprising a 70% fibervolume will more closely mimic the properties of the reinforcingelements than the properties of the injectable matrix material. Moreparticularly, FIG. 28 shows a manner by which implant strength can bevaried based on the ratio of constituent reinforcing elements (and theunderlying “fiber” that makes up the constituent reinforcing elements).Once the required strength of the composite implant is known, acomposite implant can be customized that uses an amount of distributed“fiber” reinforcing elements within the injectable matrix material. Theratio of fiber volume to matrix volume determines the ultimate strengthof the composite implant, with the strength somewhere between thestrength of the injectable matrix material and that of the reinforcingelement(s). Additionally, the form of the fibers as they are constructedwithin the reinforcing elements determines where and how that strengthis achieved. Fibers arranged in columnar axial supports (see FIG. 29)shift implant strength to compression and tension. Angular cross fibers(from a weave or braid) shift strength to bending and resistance totorsion. A mix of both results in a more balanced implant construct.

As an example, reinforcing elements of E-glass (45 GPa) braid was usedto reinforce PLA matrix (2 GPa) in a composite implant. The mix wasapproximately 55% fiber volume, therefore a composite implant wascreated with a modulus of 20-22 GPa.

By way of further example but not limitation, in orthopedics, for anon-resorbable composite implant, a stiff composite product is chosen inthe 20-80 GPa modulus range, which is appropriate in some applicationsusing a material described hereafter in the non-resorbable reinforcementelements. If the composite implant is to be fully bio-resorbable, thenthe composite implant may have a 7-45 GPa modulus range as isappropriate to splint most long bone fractures. Other polymers that mayor may not be biodegradable, such as biodegradable poly(2-hydroxyethylmethacrylate), can be used to create softer materials with engineereddirectional strengths based on the configuration of the reinforcingelements. The directions of reinforcement element fibers can creatematerials configured with lower moduli in the 500 MPa to 1 GPa range forcraniofacial fractures and other small bone repairs as needed. Inaddition, it is recognized that a combination of fibers with differentmoduli and other properties can be used to further vary the ultimatestrength of the composite implant. For instance, a glass fiber materialcould be combined with a polypropylene or PLLA material to produceappropriate moduli with the capability to be cut during manufacturingand resealed via heat treatment or the friction of the cutting blade.Additionally, a mix of bioresorbable fibers with non-bioresorbablefibers within a braided or woven reinforcement matrix would create aneventual pathway, after the material bioresorbs, for blood flow or otherfluid transit.

Additionally, in one embodiment of the invention, the reinforcingelements may be braided into geometric formations which further increaseor decrease the mechanical properties of the composite implant. By wayof example but not limitation, a composite implant with “all axial”reinforcement elements will have the highest resistance to tension andcompression, while a composite implant with braided reinforcementelements having “no axial” reinforcement elements, but includingreinforcement elements set at approximately 45° to the axis of thecomposite implant, would be strong in flexural modulus but not as strongin compression. By way of further example but not limitation, wovensheets of materials used as reinforcement elements may be designed withdiffering weave configurations to achieve similar results.

Devices, or parts of devices, that could be created using the presentinvention include, but are not limited to, fabrics such as clothing andparachutes, materials used in cars (both interiors and exteriors),vascular supports (both interior and exterior). Rigid materials such asbottles, syringes, bone-supporting materials, packaging materials,catheters, and stents may also be formed using the present invention.Consumables used in other applications, such as the abrasives used inparticle blasting for paint and rust removal, could also benefit fromthe present invention.

Preferred Method of Use

The composite implant 5 is disposed within the intramedullary canal of abone, or within another opening in the bone, so as to function as aninternal “splint”, whereby to carry the stress created during patientactivity. This allows a bone fracture to heal, or provides fortificationand/or augmentation of bone, with minimum inconvenience to the patient.The components of the composite implant 5 are introduced sequentiallyinto the patient, and assembled in-situ, thereby allowing the compositeimplant 5 to be installed using a minimally invasive approach.

In another method of use, the composite implant is pre-assembled by amanufacturer and provided to the surgeon in a sterile manner forimplantation. The fracture site would be directly accessed and thecomposite implant placed in the intramedullary canal, with or without acontainment bag. Additional injectable matrix material could be used toform-fit the composite implant to the intramedullary canal to providesignificant advantage, or the composite implant can be fixed usingmechanical means such as implant screw threads, press-fit in the canal,or another form of bone cement.

By way of example but not limitation, the composite implant 5 may beused in the following manner to treat a fracture in the tibia.

Looking now at FIG. 9, the first step is to create an access hole 50into the bone that is to be treated. If desired, an access port 52 maybe disposed in access hole 50 so as to facilitate delivering elementsthrough access hole 50. When treating fractures in long bones, the holeis made into the intramedullary canal distal to, or proximal to, thefracture site. Significantly, the modular nature of the compositeimplant means that the composite implant can be introduced into theintramedullary canal of the bone that is to be treated through an accesshole that is smaller than the final form of the composite implant. Forexample, in the case of where the composite implant is to fill anintramedullary canal that is 10 mm in diameter, the required access holemay be only 3 mm in diameter. As a result, the composite implant may bedeployed using a minimally invasive procedure that may be carried out inan office setting or surgicenter setting rather than in a conventionaloperating room. Access hole 50 is preferably drilled at an acute angleto the bone which is being treated, e.g., at an angle of approximately45 degrees, but it may be drilled at an angle anywhere between 0 degreesand 90 degrees, either proximal or distal to the fracture. This allowsthe components of the composite implant to be more easily introducedinto the intramedullary canal.

The second step is to remove or harvest the bone marrow (and/or othermatter) in the intramedullary canal, and to clean the intramedullarycanal, so as to provide a space for the composite implant 5. This isdone through the access hole 50 previously created. In one preferredform of the invention, and looking now at FIG. 10, the device forremoving or harvesting of the bone marrow from the intramedullary canalcomprises a catheter 55 with provision for introducing a liquid or gasinto the intramedullary canal and suction for removal of material fromthe intramedullary canal. The liquid or gas can be used to disrupt thecontent in the intramedullary canal or prepare the intramedullary canalfor a composite implant. The liquid or gas can be introduced in acontinuous, pulsed, or intermittent flow. A rotatable flexible rod 60,with a shaped end or attachment at the distal end (e.g., having one ormore wire loops, brushes, cutting tips, etc., which may or may not bemade out of a shape memory material such as Nitinol, and which may ormay not be steerable), is optionally used to disrupt the bone marrow inthe intramedullary canal so as to aid in the removal of the bone marrow.When harvest of the bone marrow is required, a tissue trap is utilized.FIG. 11 shows the intramedullary canal of the bone after it has beenappropriately prepared.

Looking next at FIG. 12, the third step, if needed, is to place a flowrestrictor plug 65 in the intramedullary canal distal to, and/orproximal to, where the composite implant 5 will be placed in theintramedullary canal. Again, this is done through the access hole 50previously created. Where two flow restrictor plugs 65 are used, the twoflow restrictor plugs may be connected to one another. The flowrestrictor plugs 65 may be optionally placed prior to removing orharvesting the bone marrow.

The fourth step, if needed, is to return the bone to proper alignment.

The fifth step is to introduce the containment bag 10 into theintramedullary canal via the access hole 50 previously created. In onepreferred form of the invention, and looking now at FIG. 13, thecontainment bag 10 is introduced into the intramedullary canal through adelivery catheter 70, and is releasably attached to a catheter that isused for subsequent delivery of the remaining components of thecomposite implant, i.e., the one or more reinforcement elements 15 andthe injectable matrix material 20. The catheter may have markers on itsexterior surface so as to allow the physician to determine the positionof the containment bag 10 within the bone by direct visualization of themarkers on the exterior surface of the catheter. Alternatively, and/oradditionally, containment bag 10 may have markers thereon so as to allowthe physician to determine the position of the containment bag 10 withinthe bone by indirect visualization (e.g., fluoroscopy, CT, etc.). Notethat the flexible (and compressible) nature of the containment bag 10facilitates its delivery into the intramedullary canal via a minimallyinvasive approach (i.e., via the access hole 50 previously created). Thecontainment bag 10 may comprise an auxiliary channel to allow monitoringand control of subsequent pressurization with the injectable matrixmaterial. This auxiliary channel may be parallel to the deliverycatheter, or inside the delivery catheter, or the auxiliary channel maybe at the distal end of the containment bag. Alternatively, there may bea valve at the distal end of the containment bag, or at other strategicregions of the containment bag, that can limit pressure within thecontainment bag. FIG. 14 shows containment bag 10 disposed within theintramedullary canal of the bone.

The sixth step is to sequentially introduce the one or more reinforcingelements 15 into the containment bag 10. This is done through the accesshole 50 previously created. Note that the flexible nature of thereinforcing elements 15 facilitates their delivery into the containmentbag 10 via the access hole 50 previously created. The one or morereinforcing structures 15 are preferably introduced into the containmentbag sequentially so as to build up a reinforcing mass. In one preferredform of the invention, and looking now at FIGS. 15 and 16, a pluralityof flexible reinforcing sheets 22 (in the form of concentric reinforcingtubes) are sequentially inserted into the containment bag 10, with oneflexible reinforcing concentric tube 22 being nested inside another, anda plurality of flexible reinforcing rods 35 are sequentially insertedwithin the innermost flexible concentric reinforcing tube 22 (FIGS.17-19). In one preferred form of the invention, the flexible reinforcingsheets 22 (which are preferably in the form of concentric tubes such asis shown in FIGS. 3 and 4 or rolled sheets such as is shown in FIGS. 5and 6) are delivered to the interior of the containment bag by pushingthem out of a delivery tube or, alternatively, by carrying them into thecontainment bag while held within a delivery tube and then retractingthe delivery tube, whereby to expose the flexible reinforcing sheets andallow them to expand. Preferably the size and number of flexibleconcentric reinforcing tubes 22 and reinforcing rods 35 are selected soas to meet the individual needs of a particular patient. The number offlexible concentric reinforcing tubes 22 utilized in the compositeimplant, and/or their lengths and/or cross-sectional dimensions, and/orthe number of reinforcing rods 35 used, and/or their lengths and/orcross-sectional dimensions, may be selected according to the individualneeds of a particular patient. Preferably the number, length, andcross-sectional dimensions of the reinforcing tubes, and the number,length, and cross-sectional dimensions of the reinforcing rods, areselected so as to provide a composite implant having variable stiffnessalong its length, e.g., a composite implant having a stiffer centralregion (e.g., 20 GPa) and less stiff distal and proximal ends (e.g., 3GPa), whereby to prevent stress risers from being created at the ends ofthe composite implant. To this end, the reinforcing tubes, and thereinforcing rods, are preferably provided in a variety of sizes forappropriate selection by the physician; alternatively, the reinforcingtubes and/or reinforcing rods may be sized at the time of use by thephysician. If desired, a guidewire 75 may be provided to facilitateintroduction of the one or more reinforcing elements into thecontainment bag. This guidewire 75 is preferably attached to the distalend of the containment bag 10 using an adhesive or other non-permanentattachment means. After the one or more reinforcement elements 15 havebeen placed in the containment bag, the guidewire 75 can be detachedfrom the containment bag 10 by pulling or twisting the guidewire.Alternatively, the guidewire 75 may be absorbable, in which case it maybe left in the patient at the conclusion of the procedure.

The seventh step is to introduce the injectable matrix material 20 intothe containment bag. Again this is done through the access hole 50previously created. In a preferred form of the invention the injectablematrix material is formed from two or more components that are mixedimmediately prior to injection into the patient. This may occur throughuse of a static mixer fed by multiple syringes. Alternatively thecomponents may be mixed in a remote container and then loaded into asyringe that is connected to the injection tube. In one preferred formof the invention, and looking now at FIGS. 20 and 21, an injection tube80 is used to deliver the injectable matrix material 20 into thecontainment bag 10 under pressure, where it flows over and through theone or more reinforcement structures 15 contained within the containmentbag 10. In one embodiment, the injection tube is first positioned in thedistalmost section of the containment bag, then withdrawn during theinjection process for a retro-grade fill. The injection tube 80 iswithdrawn after the matrix material is injected into the containmentbag. The injection tube is, preferably, also capable of transmitting anenergy wave into the injectable matrix material in cases where pulsatileflow or the application of vibrational forces is required to aidinjecting the matrix material into the containment bag. Vacuum may beused to facilitate wetting out of the reinforcement structures byremoval of trapped air from the composite through a secondary accesspathway within the balloon catheter.

The eighth step is for the injectable matrix material to solidify sothat the matrix material 20, the one or more reinforcing elements 15 andthe containment bag 10 become a single solidified structure 5 (FIGS. 22and 23) capable of providing support across the fracture line while thebone fracture heals. If desired, an expandable device (e.g., a balloon)may be used to provide a radial force to aid in the creation of a singleintegrated structure. Alternately, the expandable device may be abiodegradable form or feature of the injection catheter. Moreparticularly, the expandable device (e.g., balloon) may be used toenhance the penetration of the injectable matrix material into andbetween one or more reinforcing elements, the containment bag and thebone, and to enhance the interfacial bond between the injectable matrixmaterial and the one or more reinforcing elements, between theinjectable matrix material and the containment bag, and between theinjectable matrix material and the bone. In the preferred embodiments ofthe invention this solidification occurs through a chemical reactionthat proceeds at a rate that allows sufficient time for injection beforethe viscosity increases to a point where injection and flow into andaround the reinforcements is no longer possible. Generally this time isless than five to ten minutes. Most of the solidification (15-75% offull hardness) occurs within ten to sixty minutes, although with mostchemistries there will be a continuation in strength build-up over aperiod of up to five days. In the preferred chemistries the exothermicnature of the reaction is limited to minimize temperature increase inthe matrix material to less than 10 degrees C. whereby the temperatureat the bone interface is limited to <40° C.

Note how, in FIGS. 22 and 23, the composite implant can contour asneeded to the geometry of the intramedullary canal of the bone, i.e., inFIG. 22 the composite implant has a substantially linear shape to matchthe substantially linear shape of the intramedullary canal of the tibia,whereas in FIG. 23 the composite implant has a contoured shape to matchthe contour of the clavicle.

The ninth step is to close the wound.

Thus it will be seen that the present invention comprises the provisionand use of a novel composite implant for treating bone fractures (and/orfor fortifying and augmenting a bone). The composite implant is disposedwithin the intramedullary canal of the bone (or within another openingin the bone) so as to function as a “splint”, whereby to carry thestress created during patient activity. This approach allows the bonefracture to heal (or provides fortification and/or augmentation of abone) with minimum inconvenience to the patient. The composite implantcomprises a plurality of components that are introduced sequentiallyinto the patient, and assembled in situ, thereby allowing the compositeimplant to be installed using a minimally invasive approach.Significantly, the properties of the composite implant can be customtailored for different treatment situations, e.g., the composite implantcan have different lengths and/or cross-sectional dimensions, thecomposite implant can have different compressive and/or tensilestrengths, etc., all according to the individual needs of a particularpatient.

Additional Constructions

It should be appreciated that, if desired, containment bag 10 may beomitted. In this case, the one or more reinforcing elements 15 andinjectable matrix material 20 are deployed directly into theintramedullary canal (or other opening) in the bone that is beingtreated, without an intervening containment bag 10.

Furthermore, it should be appreciated that, if desired, thereinforcement rods can be placed in a deflated balloon (i.e., thecontainment bag) prior to its insertion into the body, which willeliminate the need for the surgeon/physician to separately place thereinforcement rods in the containment bag in a separate step. Thereinforcement rods can include individual braids or fibers, and/orpre-cured pins and rods (where matrix material is combined with thebraids or fibers and then pre-cured).

Furthermore, it should be appreciated that, if desired, compositeimplant 5 may be formed out of flexible reinforcing sheets 22 withoutany flexible reinforcing rods 35 (FIG. 24); with flexible reinforcingrods 35 and without any flexible reinforcing sheets 22 (FIG. 25); andwith a laminated construction comprising both flexible reinforcingsheets 22 and flexible reinforcing rods 35 (FIG. 26).

In addition, FIG. 27 shows how guidewire 75 may be used to reduce afracture prior to delivery of the composite implant. More particularly,in this form of the invention, guidewire 75 has an enlargement 85 formedat one end, with enlargement 85 being disposed exterior to the bonebeing treated, and with the opposite end 90 of guidewire 75 emergingfrom port 52. As a result of this configuration, by applying tension toend 90 of guidewire 75, the fracture can be reduced and the tensionedguidewire 75 can help support the bone. In one preferred form of theinvention, a fixture 95 may be positioned within the intramedullarycanal of the bone, adjacent to enlargement 85, so as to direct guidewire75 along the longitudinal channel of the bone and thereby facilitatefracture reduction and delivery of the composite.

It should also be appreciated that the modularity of the presentinvention and its method of use may be distributed throughout themanufacturing and/or treatment sequence, and are modifiable per anatomicuse and surgical routine. As such, a pre-cured composite implant may beused in situations where in situ curing is not desirable, or where insitu curing would unnecessarily complicate the operative procedure, orwhere a minimally invasive approach is irrelevant due to recent traumato the anatomy, including soft tissue. In this case, a bag 10 may beomitted in preference of a coating or pre-applied casing to achieveproperties such as added resistivity to solvent (water),biological-implant surface compatibility, or implant surface mechanicalproperties.

As an example, for small bone procedures such as the treatment for ahammertoe condition, an open surgical procedure is currently thepreferred technique, and a minimally invasive approach into small bonesis not highly advantageous. Metal support rods are commonly used tosupport the revision. Polymer intramedullar support rods are typicallynot strong enough to survive insertion intact. A pre-cured, smalldiameter composite implant pin, formed with the components describedherein, will have the required strength for intact insertion andmaintain enough support strength through the healing process.Additionally, a preferred embodiment is bioresorbable and may include abioresorbable surface coating as previously described.

In addition, a composite implant pin, formed in accordance with thepresent invention, may be implanted into the supporting halves of thebone and fixed in place using injectable matrix material as agap-filling adhesive (bulk filler), with the specific design of thecomposite implant pin preferably meeting the material properties of thesurrounding bone, i.e., the modulus, porosity, etc. of the surroundingbone. The use of an injectable matrix material as a gap-filling adhesive(bulk filler), with matched modulus to the bone, will eliminate stressrisers and allow natural healing-inducing strains to be applied to thebone.

In a similar manner, a pre-cured composite implant formed in accordancewith the present invention may be used to pin fractured segments of bonetogether, e.g., such as may be required with tibial fractures. Moreparticularly, the fractured segments are re-aligned, and at least onecontinuous bone tunnel (e.g., the intramedullary canal) is establishedbetween fractured segments to accept insertion of the pre-curedcomposite implant, with or without injectable matrix material being usedas bone glue. The modularity of the invention and method is maintainedwhen used in a non-minimally invasive manner. When open surgery isrequired or desired, such as with traumatic injuries or patient-specificcircumstances (e.g., osteoporosis, osteogenesis imperfecta), thecontainment bag and reinforcing elements can be assembled outside of thebody and introduced into the continuous bone tunnel (e.g., theintramedullary canal) before or after injection of the injectable matrixmaterial, then the bones are re-approximated prior to the set-up (i.e.,hardening) of the injectable matrix material. This method could includethe situation where a large composite implant, constituting asub-segment (or a series of small composite implants constituting aseries of sub-segments) was pre-cured and supplied by the manufactureras with the small bone indication above and fit to the continuous bonetunnel (e.g., the intramedullary canal) with or without a containmentbag, using a gap-filling injectable matrix material (preferably havingbone-like material properties) to secure the composite implant in place.

Mechanical shapes and fasteners can be formed around a core compositeimplant so as to form screw threads on the composite implant. Themechanical shapes and fasteners formed on the core composite implant arepreferably composed of injectable matrix material having materialproperties similar to bone. Formation of mechanical shapes and fastenershaving material properties similar to bone will reduce post-implantationthread wear and allow for natural healing due to similar strains betweenthe native bone and composite implant. Other forms of mechanical shapesand fasteners can include bent pins, clips with semi-elastic properties,bone anchors (e.g., toggling bone anchors which catch on internal bonestructure, etc.), and/or other mechanical fasteners required foranatomical (e.g., soft tissue) repairs.

It will be recognized that various methods of manufacturing may providefurther benefits to the composite implant. A pultrusion techniquewherein a resin is applied over a rolled reinforcement element sheet ora braided or woven core of reinforcement element would give the abilityto create long pins that may or may not be bioresorbable with a muchhigher modulus than that of current molded pure or blended polymerfixation elements.

In a preferred embodiment of the present invention, the geometry of thereinforcing elements are non-circular space-filling designs. A specificand preferred shape is a reinforcing element in the form of a rod havinga triangular cross-section. Multiple reinforcement elements having thisshape may be combined to form a single, larger pre-formed rod in orderto increase the fiber density inside a composite implant built up frommany stacked rods having a triangular cross-section. Rods having atriangular cross-section are advantageous in that any impact forceapplied on a single rod component will be spread across a plane ofcontact, instead of the impact force being concentrated on a pointcontact such as the case with a rod having a circular cross-section.Furthermore, the modularity of a “triangular rod” allows for stackedconfigurations of squares, trapezoids and other useful configurations tobe produced, all with very high fiber contents. Pre-formed compositeimplants can be created in a flat-rod configuration, using multiplealigned (and appropriately configured) triangular components.

Composite Implant Utilizing A Thermoplastic Polymer Injectable MatrixMaterial

In one form of the invention, the composite implant comprises athermoplastic polymer implant comprising a thermoplastic polymer matrixand a high modulus fiber component having a tensile modulus from about 8GPa to about 400 GPa.

The fiber content of the thermoplastic polymer implant may be from about5 volume percent to about 75 volume percent.

Or the fiber content of the thermoplastic polymer implant may be fromabout 25 volume percent to about 50 volume percent.

The fiber component may be selected from the group consisting of Eglass, bio glass, soluble glass, resorbable glass, carbon fiber,polyaramid fiber, PET fiber, polylactic acid homopolymer or copolymerfiber, polycaprolactone fiber, ceramic fiber, polyhydroxyalkanoatehomopolymer or copolymer fiber, PEEK fiber or combinations thereof.

And the fiber component may comprise at least one from the groupconsisting of a plurality of single filaments, woven filaments, braidedfilaments and composite mesh containing at least one compositionalfibers.

In one form of the invention, the fiber component comprises a highmodulus fiber having a modulus greater than 10 GPa compressive strengthand a low modulus thermoplastic fiber having a modulus less than 8 GPacompressive strength, and the low modulus thermoplastic fiber ispre-melted so as to provide a position-retaining structure for the highmodulus fibers.

The fiber component may have a length-to-width aspect ratio of at least20:1.

In one form of the invention, the high modulus fiber component comprisesa matrix, and the thermoplastic polymer matrix is combined with thefiber matrix via a solution-casting process.

The thermoplastic polymer matrix may be applied from a solvent solutionto a fiber construct through multiple application steps, wherein thesolvent is removed after each step so as to allow for full wetting ofthe fiber surfaces and removal of any voids from trapped solventcomponents.

The high modulus fiber component may comprise a matrix, and thethermoplastic polymer matrix may be combined with the fiber matrix via amelt coating process.

The melt coating process may be a pultrusion of a T bar fiber extrusionprocess.

The thermoplastic polymer matrix is selected from the followingbiodegradable or bioabsorbable materials: polylactic acid homopolymer orcopolymer, polycaprolactone, ceramic, polyglycolide (PGA), glycolidecopolymers, glycolide/lactide copolymers (PGA/PLA), and polylactic acidcocaprolactone block copolymer or random copolymer, polyglycolic acidcopolylactic acid block or random copolymer, glycolide/trimethylenecarbonate copolymers (PGA/TMC), stereoisomers and copolymers ofpolylactide, poly-L-lactide (PLLA), poly-D-lactide (PDLA),poly-DL-lactide (PDLLA), L-lactide, DL-lactide copolymers, L-lactide,D-lactide copolymers, lactide tetramethylene glycolide copolymers,lactide/trimethylene carbonate copolymers, lactide/delta-valerolactonecopolymers, lactide/epsilon-caprolactone copolymers, polydepsipeptide(glycine-DL-lactide copolymer), polylactide/ethylene oxide copolymers,asymmetrically 3,6-substituted poly-1,4-dioxane-2,4-diones,polyhydroxyalkanoate (PHA) homopolymer or copolymer,poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV), poly-βhydroxybutyrate (PHB), 3-polyhydroxybutytrate-co-4-polyhydroxybutyratecopolymer, 3-polyhydroxybutytrate-co-5-polyhydroxy valerate,3-polyhydroxybutytrate-co-6-polyhydroxyhexanoate,poly-3-hydroxybutyrate-co-4-hydroxybutyrate, poly-4-hydroxybutyrate(P4HB), PHB/beta-hydroxyvalerate copolymers (PHB/PHV),poly-beta.-hydroxypropionate (PHP), poly-beta-dioxanone (PDS),poly(butylene succinate) (PBS), polybutylene succinate adipate (PBSA),polyhydroxyhexanoate (PHH), polyhydroxyoctanoate (PHO),poly-DELTA-valerolactone, poly-DELTA-caprolactone, methylmethacrylate-N-vinyl pyrrolidone copolymers, polyester amides, oxalicacid polyesters, polydihydropyrans, polypeptides from alpha-amino acids,poly-beta-maleic acid (PMLA), poly-beta-alkanoic acids, polyethyleneoxide (PEO), silk, collagen, derivatized hyaluronic acid resorbable orsoluble glasses, resorbable ceramic, resorbable metal and chitinpolymers.

The thermoplastic polymer implant be constructed so that it starts todegrade in the body within about 1 month to about 24 months afterimplantation in the body.

Or the thermoplastic polymer implant may be constructed so that it losesat least 50% of its original mechanical strength after 3 months in thebody.

Or the thermoplastic polymer implant may be constructed so that it losesat least 50% of its original mechanical strength after 6 months in thebody.

Or the thermoplastic polymer implant may be constructed so that it losesat least 80% of its original mechanical strength after 12 months in thebody.

The thermoplastic polymer implant may be constructed so that about 1% toabout 25% of the thermoplastic polymer matrix is replaced by acrosslinking polymer component so as to provide improved adhesivestrength between the thermoplastic polymer matrix and the high modulusfiber component.

In one form of the invention, the high modulus fiber component comprisesa matrix, and the thermoplastic polymer matrix is applied to the fibermatrix in the form of a fine powder and then heat fused to consolidatethe subsequent molten thermoplastic polymer matrix around the highmodulus fiber component.

And in one form of the invention the high modulus fiber componentcomprises a matrix, and the thermoplastic polymer matrix is applied tothe fiber matrix via electrospinning of the thermoplastic polymer andthen heat fused to consolidate the subsequent molten thermoplasticpolymer matrix around the high modulus fiber component.

And in one form of the invention, the high modulus fiber componentcomprises a matrix, and the thermoplastic polymer matrix is applied tothe fiber matrix via electrospinning of the thermoplastic polymer matrixand the resultant voids filled with a composition which polymerizes intoa high molecular weight polymer.

The thermoplastic polymer matrix may comprise vinyl monomers which arecured using free radical initiators, UV radiation, gamma rayirradiation, or infrared radiation.

The thermoplastic polymer matrix may be cured through a condensation oraddition reaction or specialized reactions related to these and known tothose skilled in the art.

The thermoplastic polymer matrix may be cured through a urethane orepoxide resin process.

The high modulus fiber component may be coated with the thermoplasticpolymer matrix and they are then bonded together with a crosslinkingresin so as to produce the final thermoplastic polymer implant geometry.

The crosslinking resin may comprise a urethane or urea composition.

The high modulus fiber component may comprise a braided rod having atriangular cross-section.

The high modulus fiber component may comprise a braided rod having acircular cross-section.

In one form of the invention, the thermoplastic polymer implant isformed prior to implantation.

The thermoplastic polymer implant may comprise a rod having asubstantially circular cross-section.

The thermoplastic polymer implant may comprise a rod having asubstantially triangular cross-section.

The rod may be cannulated.

In one form of the invention, the cannulation is created by forming thethermoplastic polymer implant over a mandrel and then removing themandrel after the thermoplastic polymer implant is cured.

In one form of the invention, the thermoplastic polymer implantcomprises at least two high modulus fiber components each comprising abraided rod having a triangular cross-section, and the at least two highmodulus fiber components combine to form larger structures.

The thermoplastic polymer implant may be formed into a shape selectedfrom the group consisting of a screw, a rod, a pin, a nail and a boneanchor.

In one form of the invention, there is provided a method for treating abone, the method comprising: selecting at least one reinforcing elementto be combined with an injectable matrix material so as to together forma composite implant capable of supporting the bone, wherein the at leastone reinforcing element comprises a high modulus fiber component havinga tensile modulus of about 8 GPa to about 400 GPa; positioning the atleast one reinforcing element in a cavity in the bone; flowing theinjectable matrix material into the cavity in the bone so that theinjectable matrix material interfaces with the at least one reinforcingelement; and transforming the injectable matrix material from a flowablestate to a non-flowable state so as to establish a static structure forthe composite implant, such that the composite implant supports theadjacent bone.

The cavity in the bone may comprise the intramedullary canal.

The intramedullary canal may be accessed through a hole having adiameter smaller than the diameter of the intramedullary canal.

The hole may extend at an acute angle to the intramedullary canal.

The at least one reinforcing element may be flexible, and the at leastone reinforcing element may be flexed in order to pass through the holeand into the intramedullary canal.

The at least one reinforcing element may be flexible both radially andlongitudinally.

The at least one reinforcing element may comprise a plurality ofreinforcing elements, wherein each of the reinforcing elements isindividually capable of being passed through the hole, and furtherwherein the plurality of reinforcing elements collectively form astructure too large to be passed through the hole.

The at least one reinforcing element may comprise at least one from thegroup consisting of a flexible reinforcing sheet, a flexible reinforcingrod, and particulates.

The at least one reinforcing element may comprise a flexible reinforcingsheet in the form of a tube.

The at least one reinforcing element may comprise at least two flexiblereinforcing sheets arranged concentrically.

The at least one reinforcing element may comprise a flexible reinforcingsheet in the form of a rolled sheet.

The at least one reinforcing element may comprise a flexible reinforcingsheet having an arcuate cross-section.

The at least one reinforcing element may comprise a flexible reinforcingsheet having a planar cross-section.

The at least one reinforcing element may comprise a flexible reinforcingsheet comprising filaments formed into a textile.

The at least one reinforcing element may comprise a flexible reinforcingsheet comprising filaments connected by a film.

The at least one reinforcing element may comprise a flexible reinforcingrod comprising filaments held together.

The at least one reinforcing element may comprise a flexible reinforcingrod and the filaments are held together by an outer sheath.

The outer sheath may comprise filaments formed into a textile.

The at least one reinforcing element may comprise a flexible reinforcingrod and the filaments are held together by a compacted connectingstructure of a textile or film.

The connecting structure may be compacted by at least one of winding andcompressing.

The at least one reinforcing element may comprise a flexible reinforcingrod and the filaments may be held together by a binder.

The at least one reinforcing element may comprise particulates.

The at least one reinforcing element may comprise at least one flexiblereinforcing sheet and at least one flexible reinforcing rod.

The at least one flexible reinforcing sheet and the at least oneflexible reinforcing rod may be selected so as to form the compositeimplant with a desired stiffness.

The composite implant may have a stiffer central region and less stiffdistal and proximal ends.

The injectable matrix material may comprise a polymer.

The composite implant may further comprise a containment bag, and the atleast one reinforcing element may be positioned within the containmentbag after the containment bag has been positioned within the cavity inthe bone.

In another form of the invention, there is provided a method fortreating a bone, the method comprising: selecting at least one highmodulus fiber component having a tensile modulus from about 8 GPa toabout 400 GPa, wherein the at least one high modulus fiber componentcomprises a rod having a cross-section selected from the groupconsisting of round and circular; flowing an injectable matrix materialinto the cavity in the bone so that the injectable matrix materialinterfaces with the at least one high modulus fiber component so as toform a composite implant, wherein the injectable matrix materialcomprises a thermoplastic polymer matrix; and transforming theinjectable matrix material from a flowable state to a non-flowable stateso as to establish a static structure for the composite implant, suchthat the composite implant supports the adjacent bone.

The composite implant may comprise a containment bag, and the at leastone high modulus fiber component may be positioned within thecontainment bag after the containment bag has been positioned within thecavity in the bone.

In another form of the invention, there is provided a method fortreating a bone, the method comprising: selecting at least one highmodulus fiber component having a tensile modulus from about 8 GPa toabout 400 GPa, wherein the high modulus fiber component comprises aplurality of fibers, and further wherein the high modulus fibercomponent is pre-loaded with an injectable matrix material just prior toimplantation so as to together form a composite implant, wherein theinjectable matrix material comprises a thermoplastic polymer matrix;positioning the composite implant in a cavity in the bone; flowingadditional injectable matrix material into the high modulus fibercomponent so that the injectable matrix material exudes from thesurfaces of the high modulus fiber component and interfaces with thesurrounding bone cavity; and transforming the injectable matrix materialfrom a flowable state to a non-flowable state so as to establish astatic structure for the composite implant, such that the compositeimplant supports the adjacent bone and or approximated soft tissue.

Composite Implant Utilizing a Urethane Polymer Injectable MatrixMaterial

In one form of the invention, the composite implant comprises a polymerimplant comprising a high modulus fiber reinforcing component and aurethane polymer matrix.

The high modulus fiber reinforcing component may be present in an amountfrom about 10 volume percent to about 75 volume percent of the polymerimplant and wherein the modulus of the high modulus fiber reinforcingcomponent is from about 6 GPa to about 90 GPa.

The high modulus fiber reinforcing component may be selected from thegroup consisting of E glass, carbon fiber, bio glass, soluble glass,resorbable glass, ceramic fiber, and polylactic acid homopolymer andcopolymer fibers

The high modulus fiber reinforcing component may be disposed in thepolymer implant in a uniaxial direction along the major axis of thepolymer implant.

The high modulus fiber reinforcing component may comprise a woven orbraided construct.

The orientation of the woven or braided construct of the high modulusfiber reinforcing component may be held in position by a lower modulusfiber construct, wherein the lower modulus fiber construct comprises upto 10% by weight of the total high modulus fiber reinforcing componentand with the lower modulus fiber construct having a melting pointbetween about 40 degrees C. and about 200 degrees C., such that the highmodulus fiber reinforcing component is made more rigid for applicationinto the polymer implant before curing of the urethane polymer matrix.

The high modulus fiber reinforcing component may have a length-to-widthaspect ratio of at least 20:1.

The urethane injectable matrix material may be formed as described abovein the section entitled “Injectable Matrix Material”.

The urethane polymer matrix may comprise at least two individualcomponents that are mixed together to initiate the curing reaction,wherein a first component contains isocyanate functionalities and asecond component contains active hydrogen functionalities capable ofreacting with the isocyanate functionalities so as to form at least onefrom the group consisting of urethane, urea, biuret and allophonategroups during the crosslinking reaction.

The first component may be selected from the group consisting of adiisocyanate molecule, a triisocyanate molecule, a polyisocyanatemolecule having at least two isocyanate groups per molecule, anisocyanate capped polyol having at least two free isocyanate groups permolecule, an isocyanate capped polyether polyol having at least two freeisocyanate groups per molecule and an isocyanate capped polyester polyolhaving at least two free isocyanate groups per molecule.

Or the first component may be selected from the group consisting ofisophorone diisocyanate, hexamethylene diisocyanate, lysinediisocyanate, methyl lysine diisocyanate, lysine triisocyanate, toluenediisocyanate 1,2 and 1,4 and blends, methylene diphenyl diisocyanate(MDI) and polymeric MDI having an isocyanate functionality from about2.2 to about 2.8 isocyanate groups per molecule.

Or the first component may be a polyol isocyanate having a weightaverage molecular weight from about 200 to about 10,000.

Or the first component may be a blend of diisocyanate or triisocyanatemolecules with a polyol capped isocyanate having two, three or fourisocyanate groups per molecule in a ratio of about 1:99 percent byweight to about 99:1 percent by weight of the total isocyanate componentand has a viscosity at 25 degrees C. from about 250 cps to about 5,000cps.

The second component may be selected from the group consisting of apolyol having at least two hydroxyl groups and up to four hydroxylgroups per molecule where the hydroxyl groups are primary or secondaryhydroxyls, a polyether polyol having at least two hydroxyl groups and upto four hydroxyl groups per molecule, a polyester polyol having at leasttwo hydroxyl groups and up to four hydroxyl groups per molecule wherethe polyester is formed by the reaction of a diol or triol with adiacid, a polyester polyol having at least two hydroxyl groups and up tofour hydroxyl groups per molecule where the polyester is formed by thereaction of hydroxyacid which is then endcapped with a diol or triol, anaspartate molecule, an amine molecule having from at least two aminegroups to four amine groups per molecule where the amine groups are aprimary or secondary amines, alkoxylated amines having at least twoterminal amine groups per molecule, and a compound containing at leasttwo of the following: aliphatic primary hydroxyl, aliphatic secondaryhydroxyl, primary amine, secondary amine and carboxylic acid groupswithin the one molecule.

Or the polyester polyol is selected from a reaction mixture primarily ofadipic acid or other diacids with diethylene glycol, ethylene glycol orbutane diol.

The second component may be produced by the reaction product of adiamine, triamine or tetramine component with an activated vinylcomponent selected from the group consisting of dialkyl maleate, dialkylfumarate, an acrylic acid ester and vinyl ester, wherein the reactionratio is from about one equivalent of amine functionality to about oneequivalent of vinyl functionality to about four equivalents of aminefunctionality to about one equivalent of vinyl functionality.

The second component may be a blend of a polyol component and anaspartate molecule having from about 1% to about 99% polyol componentand from about 99% to about 1% aspartate, wherein at least one of thepolyol component and the aspartate molecule has a functionality towardsisocyanate of at least 2.1 active hydrogen groups per diisocyanatemolecule and a viscosity from about 250 cps to about 5000 cps at 25degrees C.

The urethane polymer matrix may be crosslinked.

The crosslinked urethane polymer matrix may be configured to startdegrading in the body within about 1 month to about 24 months afterimplantation in the body.

The crosslinked urethane polymer matrix may be configured to lose atleast 50% of its original mechanical strength after 6 months in thebody.

The crosslinked urethane polymer matrix may be configured to lose atleast 80% of its original mechanical strength after 12 months in thebody.

The polymer implant may be prepared prior to implantation.

The polymer implant may be prepared in situ.

The high modulus fiber reinforcing component may be braided and maycomprise a rod having a triangular cross-section.

The polymer implant may be prepared prior to implantation.

The high modulus fiber reinforcing component may be braided and maycomprise a rod having a circular cross-section.

The rod may be cannulated.

Cannulation may be created by forming the polymer implant over a mandreland then removing the mandrel after the implant is cured.

The polymer implant may comprise at least two high modulus fiberreinforcing components each comprising a braided rod having a triangularcross-section, and further wherein the at least two high modulus fiberreinforcing components combine to form larger structures.

The polymer implant may be formed into a shape selected from the groupconsisting of a screw, a rod, a pin, a nail and a bone anchor.

In one form of the invention, there is provided a method for treating abone, the method comprising: selecting at least one high modulus fiberreinforcing component to be combined with a urethane polymer matrix soas to together form a polymer implant capable of supporting the bone;positioning the at least one high modulus fiber reinforcing component ina cavity in the bone; flowing the urethane polymer matrix into thecavity in the bone so that the urethane polymer matrix interfaces withthe at least one high modulus fiber reinforcing component; andtransforming the urethane polymer matrix from a flowable state to anon-flowable state so as to establish a static structure for the polymerimplant, such that the polymer implant supports the adjacent bone.

The cavity in the bone may comprise the intramedullary canal.

The intramedullary canal may be accessed through a hole having adiameter smaller than the diameter of the intramedullary canal.

The hole may extend at an acute angle to the intramedullary canal.

The at least one high modulus fiber reinforcing component may beflexible, and the at least one high modulus fiber reinforcing componentmust be flexed in order to pass through the hole and into theintramedullary canal.

The at least one high modulus fiber reinforcing component may beflexible both radially and longitudinally.

The at least one high modulus fiber reinforcing component may comprise aplurality of reinforcing elements, wherein each of the reinforcingelements is individually capable of being passed through the hole, andfurther wherein the plurality of reinforcing elements collectively forma structure too large to be passed through the hole.

The at least one high modulus fiber reinforcing component may compriseat least one from the group consisting of a flexible reinforcing sheet,a flexible reinforcing rod, and particulates.

The at least one high modulus fiber reinforcing component may comprise aflexible reinforcing sheet in the form of a tube.

The at least one high modulus fiber reinforcing component may compriseat least two flexible reinforcing sheets arranged concentrically.

The at least one high modulus fiber reinforcing component may comprise aflexible reinforcing sheet in the form of a rolled sheet.

The at least one high modulus fiber reinforcing component may comprise aflexible reinforcing sheet having an arcuate cross-section.

The at least one high modulus fiber reinforcing component may comprise aflexible reinforcing sheet having a planar cross-section.

The at least one high modulus fiber reinforcing component may comprise aflexible reinforcing sheet comprising filaments formed into a textile.

The at least one high modulus fiber reinforcing component may comprise aflexible reinforcing sheet comprising filaments connected by a film.

The at least one high modulus fiber reinforcing component may comprise aflexible reinforcing rod comprising filaments held together.

The at least one high modulus fiber reinforcing component may comprise aflexible reinforcing rod and the filaments are held together by an outersheath.

The outer sheath may comprise filaments formed into a textile.

The at least one high modulus fiber reinforcing component may comprise aflexible reinforcing rod and the filaments are held together by acompacted connecting structure of a textile or film.

The connecting structure may be compacted by at least one of winding andcompressing.

The at least one high modulus fiber reinforcing component may comprise aflexible reinforcing rod and the filaments are held together by abinder.

The at least one high modulus fiber reinforcing component may compriseparticulates.

The at least one high modulus fiber reinforcing component may compriseat least one flexible reinforcing sheet and at least one flexiblereinforcing rod.

The at least one flexible reinforcing sheet and the at least oneflexible reinforcing rod may be selected so as to form the polymerimplant with a desired stiffness.

The polymer implant may have a stiffer central region and less stiffdistal and proximal ends.

The polymer implant further may comprise a containment bag, and the atleast one high modulus fiber reinforcing component may be positionedwithin the containment bag after the containment bag has been positionedwithin the cavity in the bone.

In one form of the invention, there is provided a method for treating abone, the method comprising: selecting at least one pre-formed polymerimplant created from at least one high modulus fiber reinforcingcomponent combined with a urethane polymer matrix so as to together forma polymer implant capable of supporting the bone; positioning the atleast one pre-formed polymer implant in a cavity in the bone; flowing aurethane polymer matrix into the cavity in the bone so that the urethanepolymer matrix interfaces with the at least one pre-formed polymerimplant; and transforming the urethane polymer matrix from a flowablestate to a non-flowable state so as to establish a static structure forthe polymer implant, such that the polymer implant supports the adjacentbone.

The polymer implant may further comprise a containment bag, and the atleast one high modulus fiber reinforcing component may be positionedwithin the containment bag after the containment bag has been positionedwithin the cavity in the bone.

In one form of the invention, there is provided a method for treating abone, the method comprising: selecting at least one high modulus fiberreinforcing component which is pre-loaded with a urethane polymer matrixjust prior to implantation so as to together form a polymer implantcapable of supporting the bone once fully cured; positioning at leastone high modulus fiber reinforcing component in a cavity in the bone;flowing additional urethane polymer matrix into the at least one highmodulus fiber reinforcing component so that the urethane polymer matrixexudes from the surfaces of the at least one high modulus fiberreinforcing component and interfaces with the surrounding bone cavity;and transforming the urethane polymer matrix from a flowable state to anon-flowable state so as to establish a static structure for the polymerimplant, such that the polymer implant supports the adjacent bone and orapproximated soft tissue.

Composite Implant Utilizing a Resin Injectable Matrix Material

In one form of the invention, the composite implant comprises a highmodulus fiber reinforcing component and resin injectable matrixmaterial.

The high modulus fiber reinforcing component may be of the sortdisclosed above.

The resin injectable matrix material may be an acrylic resin compositioncomprising a mixture of prepolymerized acrylic resins or styrene acrylicresins having molecular weights from about 200 to 20,000 daltons andacrylic monomers selected from at least one of the following:methacrylic acid, methyl methacrylate, ethyl methacrylate, butylmethacrylate, acrylic acid, methyl acrylate, ethyl acrylate, butylacrylate ethylene glycol diacrylate, ethylene glycol dimethacrylate,trimethylol propane triacrylate and trimethylol propanetriamethacrylate, and an organic peroxide free radical initiator, withthe mixture having an initial viscosity from about 200 cps to about 5000cps at 20-25 degrees C. The acrylic resin composition described abovemay also have additional additives such as inorganic fillers,stabilizers to prevent cure of the acrylic monomers during storage andactivators to accelerate the free radical cure of the acrylic system.

The resin matrix may also be a polyurethane having terminal isocyanatefunctionality and a viscosity from about 800 cps to about 10,000 cps atthe temperature when the urethane resin matrix is applied to the highmodulus fibers and a viscosity of at least 50,000 cps at 20-25 degreesC. In a non-in situ embodiment, the resin matrix may have a terminalisocyanate functionality and be applied to the high modulus fiber at atemperature from about 100 degrees C. to about 200 degrees C., the highmodulus fiber having been surface coated with a sizer or primer thatprovides additional adhesion between the urethane resin matrix and thehigh modulus fiber and can optionally act as a secondary catalyst forfurther molecular weight increase of the urethane resin matrix andadhesion to the high modulus fiber.

In one form of the present invention, the composite implant comprises aresin matrix and a high modulus fiber reinforcing component, wherein thecompressive modulus ratio between the cured resin injectable matrixmaterial and the high fiber reinforcing component is from about 1:3 toabout 1:20, and the flexural modulus ratio between the cured resininjectable matrix material and the high fiber reinforcing component isabout 1:3 to about 1:10. The resin injectable matrix material may beapplied to the high modulus fiber component of the composite implant ina continuous process, with the resin injectable matrix material having aviscosity (at application temperature) of from about 2 Pas to about 2000Pas, with fiber content of from about 5 volume percent to about 75volume percent. The high fiber reinforcing component may be selectedfrom at least one of the following materials: E-glass, bio glass,soluble glass, resorbable glass, carbon fiber, polyaramid fiber, PETfiber, ceramic fiber, PEEK fiber, fibers formed from homopolymers orcopolymers of one or more monomers selected from D lactic acid, L lacticacid dilactides of D and L isomers, glycolic acid, and/or combinationsthereof.

In another embodiment of the present invention, the composite implantcomprises a high fiber reinforcing component which comprises a series ofsingle filaments, woven filaments or a composite mesh containing one ormore different compositional fibers. The high modulus fiber reinforcingcomponent may comprise a very high modulus fiber (e.g., a fiber having amodulus greater than about 80 GPa compressive strength) and a lowmodulus thermoplastic fiber (e.g., a fiber having a modulus less than 8GPa), where the thermoplastic fiber is pre-melted so as to provide aretaining structure for the rigid fibers.

In another embodiment of the composite implant, the resin injectablematrix material is an acrylic resin composition comprising a mixture ofprepolymerized acrylic resins (or styrene acrylic resins) havingmolecular weights from about 200 to 20,000 daltons, and acrylic monomersselected from at least one of the following: methacrylic acid, methylmethacrylate, ethyl methacrylate, butyl methacrylate, acrylic acid,methyl acrylate, ethyl acrylate, butyl acrylate ethylene glycoldiacrylate, ethylene glycol dimethacrylate, trimethylol propanetriacrylate and trimethylol propane triamethacrylate, and an organicperoxide free radical initiator, with the mixture having an initialviscosity from about 200 cps to about 5000 cps at 20-25 degrees C. Theacrylic resin composition described above may also comprise additionaladditives, e.g., inorganic fillers, stabilizers to prevent cure of theacrylic monomers during storage, and/or activators to accelerate thefree radical cure of the acrylic system. The high modulus fiberreinforcing component may have a surface which is coated with a sizingagent, or a primer, which provides additional adhesion between theacrylic resin matrix and the high modulus fiber reinforcing component,and which can optionally act as a secondary catalyst for thepolymerization of the acrylic monomers. In addition, the high modulusfiber reinforcing component may be surface coated with an aminofunctional material selected from at least one of the followingmaterials: amino silanes, lysine, polyamines, amino acids and polyaminoacids.

In another embodiment of the present invention, the resin injectablematrix material comprises a polyurethane having terminal isocyanatefunctionality and a viscosity from about 800 cps to about 10,000 cps (atthe temperature when the urethane resin matrix is applied to the highmodulus fiber reinforcing component) and a viscosity of at least 50,000cps at 20-25 degrees C. The resin injectable matrix material may alsocomprise a polyurethane having terminal isocyanate functionality, whichis applied to the high modulus fiber at a temperature from about 100degrees C. to about 200 degrees C. The high modulus fiber reinforcingcomponent may be surface coated (e.g., with a sizer or primer) thatprovides additional adhesion between the urethane resin injectablematrix material and the high modulus fiber reinforcing component, andwhich can optionally act as a secondary catalyst for further molecularweight increase of the urethane resin injectable matrix material and canfacilitate adhesion to the high modulus fiber. The high modulus fiberreinforcing component may also be surface coated with an aminofunctional material selected from at least one of the followingmaterials: amino silanes, lysine, polyamines, amino acids, and polyaminoacids.

In another embodiment of the present invention, the resin injectablematrix material is a polyurethane, and the composite implant may alsocontain residual isocyanate groups in the composite structure such thatthey can be stored in a dry inert atmosphere without furthercrosslinking reactions, and then, when applied in the body (i.e., wheremoisture is present), will further cure until no residual isocyanategroups are present. This composite implant may also comprise up to about4% by weight of polymer-bound isocyanate groups in the structure and/orthe composite implant may provide a foamed surface structure in the bodyduring final cure so as to accommodate the special difference betweenthe polymer implant and the cavity constructed to accommodate thepolymer implant, thus providing improved strength and stiffness to therepaired bone area.

Bioresorbable and Biodegradable Composite Materials

In another form of the invention, there is provided a composition ofmatter that results in high modulus composite materials that are capableof biodegrading or bioabsorbing due to ambient (e.g., bodily orenvironmental) conditions. The utility of the materials range from theaforementioned medical implants to other medical devices (e.g.,syringes) to a wide variety of non-medical applications, e.g., packagingmaterials (such as packages, packaging, disposable pallets, etc.),landscaping films, trash bags, etc.

More particularly, the removal and handling of waste products is acommon issue faced by local and federal municipalities within manycountries. Land fill availability, accessibility, and restrictions havecreated the need for complex re-cycling programs at increased expense totaxpayers and governments.

The rapid technological innovations in polymer processing and formingfor structural development has led to increases in long-life wastematerials, taking decades to millennia to degrade, therefore requiringvery extensive re-cycling programs or potentially polluting reductionmeans such as through burning or solvent reactions. In addition, andfrequently, the usable life spans of the polymer structures are low dueto limitations in the material properties. Non-degradable polymers arevery quickly manufactured through processes such as injection molding,extrusion, pultrusion, heat pressing, etc., however, the final materialmay not be strong enough for some applications. The polymers can bestrengthened through the addition of high modulus fiber particles,however, the resulting increase in stiffness is usually offset by makingthe material brittle. Full composites are designed to provide thetargeted strength profiles for very long life or high strength materialsthat polymers alone do not provide, however, they are commonlyassociated with the difficulty in waste management previously described.

Current degradable polymers are effective but are limited inapplications due to strength limitations. The addition of soluble highmodulus particulate serves to stiffen the material but adds abrittleness as described above.

Thus it will be seen that a new approach is needed for reducing theburden of waste management on society at large.

The present invention provides a new approach for creating high strengthmechanical structures for materials with defined useful life-cycles thatwill biodegrade or bioabsorb due to the normal environment envisioned atend of life.

The present invention also provides a new approach for using suchmaterial degradation to provide utility or delivery of a localalteration of environmental conditions.

More particularly, the present invention comprises the provision and useof a novel composite comprising a biodegradable or bioabsorbableflowable polymer (i.e., the injectable matrix material, sometimesreferred to simply as “the matrix”) and a high modulus reinforcingelement to create useful structures. The composite is created from atleast one reinforcing element, embedded within a matrix. The finalcomposite structure can be either anisotropic or isotropic, depending onthe requirements of the final construct. The final composite issusceptible to complete or partial degradation or dissolution due toambient (e.g., bodily or environmental) conditions including, but notlimited to, immersion in water, saline (physiologic, oceanographic,etc.), the presence of naturally-occurring or intentionally-addedenzymes or chemicals, etc. Preferably, the materials are designed fortheir working environment. As an example, structural storage of foodgoods, once depleted, may be designed to rapidly degrade in high saltcontent water such as the ocean, allowing ocean-going vessels to reducewaste without adversely affecting the environment.

Furthermore, the present invention is capable of degrading intosub-components engineered such that the local area (e.g., the body orthe environment) is beneficially affected. The duration, intensity, andsequence of the release of remnants of the degradation process can bedesigned to produce pH shifts in a local area (e.g., the body or theenvironment) or to release other compounds into the local area (e.g.,the body or the environment). For example, during the degradation of acomposite structure, there may be a rapid release of remnants for aburst of either acidic or basic pH shift, followed at a later period oftime by the release of buffering solutions to re-alter the local area(e.g., the body or the environment). As a more specific example, abio-degradable textile may be produced that is highly flexible buttensile-reinforced. The textile, in the form of a fabric, may bedesigned for coverage over garden materials as initial protectivebarriers that degrade over a time period of weeks into either basic oracidic materials beneficial to the plant material below the protectivebarrier. High tensile strength allows the composite material to bespread over large areas by industrial mechanisms without fear of tearingthe protective material.

The matrix material is preferably polymeric and preferably bioabsorbableand/or biodegradable. The matrix material may be an organic polymer thatcan be formed via a polymerization process and/or the matrix materialmay also comprise a bioactive filler material and/or a degradation ordeposition agent.

The reinforcement material is preferably a bio-degradable,water-soluble, bio-absorbable or carbon-neutral material with a modulusengineered for higher tensile or compressive properties than thesurrounding matrix material. The reinforcing elements can beparticulate, nano-sized, or fiberous in nature, preferably with anaspect ratio of from about 1:5 to >1:100.

The reinforcing elements can be coated with another material thatprovides, but is not limited to, one of more of the following features:enhanced bonding to the matrix material; increase in reinforcementdimensions; modulation of hydro-diffusion access to the reinforcementmaterial, etc.

Optionally, the matrix material may contain a biocompatible solvent,with the solvent reducing viscosity so as to allow the matrix materialto flow easily, and with the solvent thereafter diffusing from thecomposite so as to facilitate or provide stiffening and/or to impart oralter the porosity of the matrix material.

Thus it will be seen that the present invention comprises a new approachfor creating high strength composite structures with defined usefullife-cycles that will biodegrade or bioabsorb due to the normalenvironment envisioned at the end of life.

The present invention also provides a new approach for using thiscomposite degradation to provide utility, including the delivery of alocal alteration of the host area (e.g., the body or the environment).

One preferred embodiment is the use of a thermoplastic matrix-basedcomposite with disparate reinforcing elements, the mix of which providesincreased material strength and advantages in chemical interactions suchthat degradation time and the effects on the local area (e.g., body orenvironment) are controlled.

In another preferred embodiment, a thermosetting matrix material iscombined with disparate reinforcing elements, the mix of which providesincreased material strength and advantages in chemical interactions suchthat degradation time and the effects on the local area (e.g., body orenvironment) are controlled.

The present invention provides a new approach for creating high strengthcomposite structures with defined useful life-cycles that willbiodegrade or bioabsorb due to the normal environment envisioned at endof life.

The present invention also provides a new approach for using suchmaterial degradation to provide utility or the delivery of a localalteration of the host area (e.g., the body or environment) conditions.

Composite Material.

The present invention comprises the provision and use of a novelcomposite comprising a biodegradable or bioabsorbable flowable polymer(i.e., the matrix) and biodegradable or bioabsorbable high modulusreinforcing elements to create useful composite structures. In onepreferred form of the present invention, the composite comprises athermoset (i.e., the matrix) with high modulus, high bioglass content(i.e., the reinforcing elements). The composite is preferably configuredfor liquid injection and subsequent setting, although it may also bepreformed. In one preferred form of the invention, the matrix comprisespolyurethane due to its promotion of high strength and biodegradability.The composite comprises at least one reinforcing element, embeddedwithin a matrix. The final composite material can be either anisotropicor isotropic, depending on the requirements of the final construct. Thefinal composite is susceptible to complete or partial degradation ordissolution due to the host area (body or environmental) conditionsincluding, but not limited to, immersion in water, saline (physiologic,oceanographic, etc.), the presence of naturally-occurring orintentionally-added enzymes or chemicals. Preferably, the composite isdesigned for its work environment. As an example, structural storage offood goods, once depleted, may be designed to rapidly degrade in highsalt content water such as the ocean, allowing ocean going vessels toreduce waste without adversely affecting the environment.

Options of final practical use may include pre-cured objects requiringsignificant but sub-metal structural strength. The invention lendsitself to modular assembly with a thermoplastic or thermoset such as apolyurethane thermoset adhesive. The present invention also lends itselfto substantially any application wherein the embedded reinforcingelements have their access to water restricted prior to the desiredpoint of elimination, at which time water access to the bioabsorbablefiber releases ions as agents that change the pH and assist catalytichydrolysis of the polyurethane and the subsequent biodegradationaccording to established test methods like ASTM D6400, D7081, etc.

In a preferred form, bioabsorbable glass (i.e., the reinforcingelements) is present from about 5 Vol % to about 65 Vol % of thecomposite. Since this is a biodegradable process, ordinary glass andother ceramic/metal fibers (including carbon fiber, carbon fibrils andcarbon nanoparticles), which are not considered to be organic carbon,are not included in the organic carbon biodegradation process.Therefore, the reinforcing elements can also include inorganic particlesthat may or may not act as further agents for degradation such as, butnot limited to, fibers and particles of wollastonite, talcs, clays,metal silicates, etc.

In the present invention, a set of bio-degradable ingredients are usedto produce materials with higher moduli than a bio-degradable polymeralone, even when reinforced with fiber particles. The composite isformed from the basic building blocks of the matrix and reinforcingelements, wherein the reinforcing elements may be formed using textileengineering techniques and primarily continuous, bio-degradable,bio-resorbable or bio-neutral fibers.

Multiples of these fibers (i.e., the reinforcing elements), preferablewith aspect ratios of at least 20:1 (length to width), are preferablyused to form structures capable of being completely immersed and bondedwith a thermoset-, thermoplastic- or acrylic-based bio-degradable,bio-resorbable or bio-neutral matrix material to form a desired shapeonce the matrix material has been transformed from a flowable tonon-flowable state.

The required strength of the composite can be customized and distributedby using an appropriate amount of distributed “fiber” reinforcingelements within the homogeneous matrix. The ratio of fiber volume:matrixvolume proportionately determines the ultimate strength of thestructure. Additionally, the form of the fibers as they are constructedwithin the reinforcing elements determines where and how that strengthis achieved. Fibers arranged in columnar axial supports shift implantstrength to compression, tension, and bending. Angular cross-fibers(termed bias, often seen in weaving or braids) shift strength totorsional resistance and hoop strength, thereby reducing the risk ofcatastrophic failures.

Matrix Material.

The matrix material is preferably polymeric and bioabsorbable and/orbiodegradable in response to regional (bodily or environmental) stimulisuch as, but not limited to, water, saline, and naturally orartificially-introduced enzymes. The matrix material may be a syntheticpolymer or an organic polymer that can be formed via a polymerizationprocess flowable under thermoplastic processes, a polymer requiringthermosetting processes or acrylic materials. The matrix may alsocomprise a bioactive filler material and/or a degradation or depositionagent.

In one preferred embodiment, the matrix is a thermoplastic solutionwhere the introduction of bioabsorbable glass and bioglass (i.e., thereinforcing elements) assists the ambient hydrolytic breakdown ofbiodegradable polymers which are currently only broken down at elevatedtemperatures. Thus, the use of such reinforcing elements to acceleratethe hydrolytic breakdown of the matrix material is particularlyadvantageous where effective hydrolysis must take place at bodilytemperatures or temperatures acceptable to the local environment.Polymers specifically sensitive to this inventive approach include, butnot limited to, are polylactic acid homo and copolymers,polycaprolactone, polybutylene succinate homo and copolymers,polybutylene succinate co adipate, polyethylene glycol terephthalate coadipate, poly butylene glycol adipate co terephthalate, etc. Typically,catalytic levels or sub 10% levels of bioabsorbable glass is used inthese applications in powder, chopped fiber or continuous fiber form.

The thermoplastic composite system may also include 0.1% to 20% of aninorganic material that, when immersed in an aqueous environment attemperatures of about 5 degrees C. to about 40 degrees C., and having apH from 5.5 to 8, will result in the aqueous micro-environment of thecomposite component to change by at least 0.5 pH, and preferably about1.5 to 3 pH, thus accelerating the hydrolytic breakdown of the matrix(e.g., polyester or polyester polyurethane) components so that themolecular weight is reduced by a factor of 4 to 20 in the definedtimescale, making the residual low molecular weight fragments extremelybrittle in nature and susceptible to microbial attack.

The matrix material may also be a multi-component polymer system that ismixed immediately prior to final structural formation. Optionally, thematrix material may contain a biocompatible solvent, with the solventreducing viscosity so as to allow the matrix material to flow easier,and with the solvent thereafter rapidly diffusing so as to facilitate orprovide stiffening or curing of the composite structure. The solvent mayalso be used to alter the porosity of the matrix material.

In one preferred embodiment of the present invention, polyurethanes areused as the matrix material, although other suitable chemistry systemswill be apparent to those skilled in the art. The polyurethanes areproduced through the reaction of difunctional, or multifunctional, orpolyfunctional, isocyanate molecules having at least two reactivefunctional groups per molecule, with a difunctional or multifunctionalcompound containing two or more active hydrogen (including water) groupscapable of reacting with an isocyanate group, such active hydrogengroups may include primary and secondary aliphatic hydroxyl materialsand amines, primary, secondary and aromatic amine, aliphatic andaromatic thiols, urethane and urea groups.

Suitable isocyanates useful in the practice of this invention include,but are not limited to, aromatic diisocyanates such as 2,4-toluenediisocyanate, 2,6-toluene diisocyanate, 2,2′-diphenylmethanediisocyanate, 2,4′-diphenylmethane diisocyanate, 4,4′-diphenylmethanediisocyanate, diphenyldimethylmethane diisocyanate, dibenzyldiisocyanate, naphthylene diisocyanate, phenylene diisocyanate, xylylenediisocyanate, 4,4′-oxybis(phenylisocyanate) or tetramethylxylylenediisocyanate; aliphatic diisocyanates such as tetramethylenediisocyanate, hexamethylene diisocyanate, dimethyl diisocyanate, lysinediisocyanate, lysine triisocyanate, methyl lysine diisocyanate,2-methylpentane-1,5-diisocyanate, 3-methylpentane-1,5-diisocyanate or2,2,4-trimethylhexamethylene diisocyanate; and alicyclic diisocyanatessuch as isophorone diisocyanate, 4, 4′ methylene bis(cyclohexylisocyanate) (HMDI) cyclohexane diisocyanate, hydrogenated xylylenediisocyanate, hydrogenated diphenylmethane diisocyanate, hydrogenatedtrimethylxylylene diisocyanate, 2,4,6-trimethyl 1,3-phenylenediisocyanate.

The present invention comprises the use of these same multi-functionalisocyanates with multifunctional amines or multifunctional substitutedamines, multifunctional ketimines, multifunctional aldimines,isocyanurates or biurets. By way of example but not limitation, suchmultifunctional amines may include hexamethylene diamine, isophoronediamine, and lysine. Examples of substituted amines may includeN-substituted diaspartic acid derivatives. Examples of multifunctionalketimines and aldimines may be made from the multifunctional aminesmentioned previously and methyl isobutyl ketone or isobutyraldehyde.

When a biodegradable implant is desired, the aliphatic isocyanates aregenerally favored. In one embodiment of the present invention, thealiphatic isocyanates are preferred.

In a preferred embodiment of the present invention, the isocyanatecomponent is reacted with a polyol to produce a polyurethane. Suitablepolyols include, but not limited to, polycaprolactone diol andpolycaprolactone triol. Suitable dihydroxy compounds which may beutilized in the practice of this invention include, but are not limitedto, ethylene glycol, propylene glycol, butylene glycol, hexylene glycoland polyols including polyalkylene oxides, polyvinyl alcohols, and thelike. In some embodiments, the polyol compounds can be a polyalkyleneoxide such as polyethylene oxide (“PEO”), polypropylene oxide (“PPO”),block or random copolymers of polyethylene oxide (PEO) and polypropyleneoxide (PPO). Higher functional polyol compounds are also useful and caninclude glycerin, 1,2,4-butanetriol, trimethylol propane,pentaerythritol and dipentaerythritol,1,1,4,4-tetrakis(hydroxymethyl)cyclohexane. Other useful polyolsactivehydrogen containing molecules can include ethanolamine, diethanolamine,triethanol amine and N,N,N′,N′-Tetrakis(2-hydroxyethyl)ethylenediamine),ethylene diamine, diethylene triamine, triethylene tetramine,tetraethylene pentamine, aspartate reaction products of a vinyl esterwith a diamine, triamine or tetramine such as diethyl maleate, diethylfumarate, acrylate and methacrylate esters with a diamine or triaminemolecule.

The polyol materials discussed above may be used alone or, optionally,as mixtures thereof. The foregoing materials are merely examples ofuseful components for producing polyurethanes and should not be viewedas a limitation of the present invention. These higher functional polyolmaterials will produce highly cross-linked polyurethanes with highhardness and stiffness.

In preferred embodiments, the multifunctional hydroxyl material mayinclude at least one bioabsorbable group to alter the degradationprofile of the resulting branched, functionalized compound.Bioabsorbable groups which may be combined with the multifunctionalcompound include, but are not limited to, groups derived from glycolide,glycolic acid, lactide, lactic acid, caprolactone, dioxanone,trimethylene carbonate, and combinations thereof. For example, in oneembodiment, the multifunctional compound may include trimethylol propanein combination with dioxanone and glycolide. Methods for addingbioabsorbable groups to a multifunctional compound are known in the art.Where the multifunctional compound is modified to include bioabsorbablegroups, the bioabsorbable groups may be present in an amount rangingfrom about 50 percent to about 95 percent of the combined weight of themultifunctional compound and bioabsorbable groups, typically from about7 percent to about 90 percent of the combined weight of themultifunctional compound and bioabsorbable groups. The multifunctionalcompound can have a weight (average molecular weight, all listed inkilodaltons) ranging from about 500 to about 50,000, typically fromabout 1,000 to about 3,000, and typically possesses active hydrogenfunctionality ranging from at least 2 to about 6, preferably from 2 toabout 4.

In one preferred embodiment of the present invention, thepolycaprolactone diols and, triols and tetrols provide branching sitesfor polyurethanes that are biodegradable.

The isocyanate is reacted with a polyol to produce a prepolymer. Methodsfor endcapping the polyol with an isocyanate are known to those skilledin the art. For example, a polycaprolactone diol may be combined withisophorone diisocyanate by heating to a suitable temperature rangingfrom about 55 degrees C. to about 80 degrees C., typically about 70degrees C. The resulting diisocyanatefunctional compound may then bestored until combined with additional polyol to form the finalpolyurethane product.

Reaction of the urethane prepolymer with polyol to form the finalpolyurethane product generally requires a catalyst to provide convenientworking and cure times. Polyurethane catalysts can be classified intotwo broad categories, amine compounds and organometallic complexes. Theycan be further classified as to their specificity, balance, and relativepower or efficiency. Traditional amine catalysts have been tertiaryamines such as triethylenediamine (TEDA, also known as1,4-diazabicyclo[2.2.2]octane or DABCO (a trademark of Air Products),dimethylcyclohexylamine (DMCHA), and dimethylethanolamine (DMEA).Tertiary amine catalysts are selected based on whether they drive theurethane (polyol+isocyanate, or gel) reaction, the urea(water+isocyanate, or blow) reaction, or the isocyanate trimerizationreaction (e.g., using potassium acetate, to form isocyanurate ringstructure). Since most tertiary amine catalysts will drive all threereactions to some extent, they are also selected based on how much theyfavor one reaction over another.

Another useful class of polyurethane catalysts are the organometalliccompounds based on mercury, lead, tin ((for example dibutyl tindilaurate), bismuth ((for example bismuth octanoate), titanium complexesand zinc. Dibutyl tin dilaurate and stannous octoate are widely usedcatalysts in many polyurethane formulations. Other catalysts includetertian amines such as triethylene diamide. Mixtures of organometalcatalysts and blends of Tertian amines can be used to obtain thepreferred gelling profile. Applicable catalyst concentrations preferablyrange from 0.01% to 4% based on polyol content.

Reinforcing Elements.

The reinforcing elements preferably comprise a biodegradable,water-soluble, bio-absorbable or carbon-neutral material with a modulusengineered for higher tensile or compressive properties than thesurrounding matrix. The reinforcing elements may also be a mix ofdifferent materials with varying strength and degradation profiles asrequired for the final structure or its end of life degradationenvironment. Additionally the reinforcement materials may be chosen fromstructural members constructed using textile processing means, randomlyoriented fibers, chopped fibers, or nano-size or greater particulates.

Where the reinforcement elements comprise a textile, its reinforcingproperties and degradation profile may be modified by changing thematerials, orientation, length, shape, volume, twist, and angle of thefibers and filaments within the textile of the reinforcing elements. Thefibers and filaments in a textile are preferably continuous with a highaspect ratio (length:width) preferably greater than 20:1. With thepresent invention, a preferred generic configuration is one with highaxial fiber counts in relative balance with the biasing fiber counts andbias fiber angle. The preferred axial fiber:bias fiber ratio is between10:90 and 90:10, depending on the desired properties. The bias fiberangle is important for additional support as tensors splitting intoadditional axial support and torsional and burst resistivity; they areusually set at an acute angle to intersecting fibers and filaments, butthe angle may vary between 0 degrees and 90 degrees or random. Inaddition, the bias fibers may be used to add hydrostatic pressure todraw flowable matrix into the center of non-planar reinforcing elementsand to aid in the final cross-sectional shape without altering theoverall cross-sectional footprint. It will be readily understood by anindividual skilled in the art that further changes to the geometry of atextile engineered reinforcement element can modify the physicalcapabilities of the final product including braiding the reinforcingelement over a removable mandrel to produce a cannulated finalreinforcing element or weaving reinforcing planes for the use with lowmodulus, high ductility matrices for flexible sealing fabrics.Additional design changes include, but are not limited to, changing theorientation of one or more of the reinforcing elements, and/or bychanging the volume of one or more of the reinforcing elements. Inaddition, a textile-based reinforcing element may have the fiber volumeand/or direction and/or weave and/or braid altered along its length inorder to create the variable stiffness, wettability or other physicalproperties desired for the composite structure.

In one preferred form of the invention, the one or more reinforcingelements comprise from about 5% to 75% (by volume) of the compositeimplant, typically at least 20% (by volume) of the composite implant.

Examples of suitable biodegradable or bioabsorbable filaments, fibers,and particulates used to form the aforementioned reinforcing elementsinclude, but are not limited to, polyglycolic acid (PGA), glycolidecopolymers, glycolide/lactide copolymers (PGA/PLA),glycolide/trimethylene carbonate copolymers (PGA/TMC), stereoisomers andcopolymers of polylactide, poly-L-lactide (PLLA), poly-D-lactide (PDLA),poly-DL-lactide (PDLLA), L-lactide, DLIDF-lactide copolymers, L-lactide,D-lactide copolymers, lactide tetramethylene glycolide copolymers,lactide/trimethylene carbonate copolymers, lactide/δ-valerolactonecopolymers, lactide/ε-caprolactone copolymers, polydepsipeptide(glycine-DL-lactide copolymer), polylactide/ethylene oxide copolymers,asymmetrically 3,6-substituted poly-1,4-dioxane-2,4-diones,polyhydroxyalkanaote homopolymers, copolymers, terpolymers such as poly3 hydroxybutyrate co 3 hydroxyvalerate poly 3 hydroxybutyrate co 4hydroxybutyrate, polylactic acid co caprolactone, polylactic acid coglycolic acid co caprolactone block and randon copolymerspoly-beta-dioxanone (PDS), poly-DELTA-valerolactone,poly-δ-caprolactone, methyl methacrylate-N-vinyl pyrrolidone copolymers,polyester amides, oxalic acid polyesters, polydihydropyrans,polypeptides from alpha-amino acids, poly-beta-maleic acid (PMLA),poly-β-alkanoic acids, polyethylene oxide (PEO), silk, collagen,derivatized hyaluronic acid, resorbable or soluble glasses, resorbableceramic, resorbable metal and chitin polymers.

By way of further example but not limitation, suitable bio-neutralmaterials include natural polyesters and silks, polyvinyl alcohol,glass, ceramic, metal, and carbon fiber.

In addition, the reinforcing elements may be constructed of a variety ofdifferent fibers with different properties. For example, a thermoplasticfiber may be interwoven within portions of a higher modulus material inorder to facilitate handling during cutting operations with a hot knifeor, through the use of a heat gun, to reduce filament damage duringstorage.

Coatings for the Reinforcing Elements.

The reinforcing elements may be coated (also called sized) with anappropriate material that provides, but is not limited to, one of moreof the following features: enhanced bonding to the matrix material;increase in reinforcement dimensions; modulation of hydro-diffusionaccess to the reinforcement material.

Compatibility among the specific components that comprise a compositestructure is essential in order to ensure optimal interfacial bonding,mechanical properties, physical properties, and degradation rates.Compounds known as coupling agents, compatibilizers, or sizings, whichmay be incorporated into the components of the composite, serve toenhance the chemical bonding between the specific components of thecomposite implant. In a preferred embodiment, the interfacial bondstrength between the reinforcing elements and the matrix material can beenhanced through the addition of a variety of compatibilizers, e.g.,calcium phosphate, hydroxyapatite, calcium apatite, fused-silica,aluminum oxide, apatitewollastonite glass, bioglass, compounds ofcalcium salt, phosphorus, sodium salt and silicates, maleic anhydride,diisocyanatediisocyanates, epoxides, silanesilanes, and celluloseesters. These agents may be incorporated into, and/or applied to, thecomponents of the composite through a number of methods, e.g., plasmadeposition, chemical vapor deposition, dip coating, melt-blending, spinor spray-on. A specific example is the application of an alkyl, alkoxysilane and organo titanate coupling agent to glass fiber reinforcementin order to increase its interfacial bonding strength with theinjectable matrix material.

In one preferred form of the invention, the composite is capable ofdegrading into sub-components engineered such that the host area (e.g.,the body or the local environment) is beneficially affected. Theduration, intensity, and sequence of the release of remnants of thedegradation process can be designed to produce pH shifts in a localenvironment or to release other compounds into the local environment.For example, during the degradation of a material structure, there maybe a rapid release of remnants for a burst of either acidic or basic pHshift, followed at a later period of time by the release of bufferingsolutions to re-alter that environment. As a more specific example, abio-degradable textile may be produced that is highly flexible buttensile-reinforced for strength. The textile, in the form of a fabric,may be designed for coverage over garden materials as initial protectivebarriers that degrade (over a time period of weeks) into either basic oracidic materials beneficial to the plant located below the protectivebarrier. High tensile strength allows the composite to be spread overlarge areas by industrial mechanisms without fear of tearing.

Additions To Matrix.

If desired, both the matrix material and the reinforcing elements mayalso comprise a bioactive filler material.

Fillers.

The matrix material may include a filler in the form of biocompatibleparticles. The first or primary filler, preferably in the form ofparticles, may also provide porosity and enhanced permeability or poreconnectivity. One suitable particulate filler material is tricalciumphosphate, although other suitable filler materials will be apparent tothose skilled in the art such as orthophosphates, monocalciumphosphates, dicalcium phosphates, tricalcium phosphates, andcombinations thereof. Also biodegradable glasses can be utilized as afiller.

The filler particles may comprise a degradable polymer such aspolylactic acid, polyglycolic acid, polycaprolactone and co-polymersthereof. The particles may also comprise degradable polymer containingone or more inorganic fillers.

In one embodiment the inorganic filler particles have mean diametersranging from about 1 micron to about 20 microns.

In another embodiment the porosity and compressive properties of thematrix material may be modified by using additional fillers that may beinorganic, organic or another suitable bio-neutral or biodegradablematerial. Such refinements include the addition of particles having meandiameters ranging from about 10 nm to about 50 microns or more,preferably from about 1 micron to 20 microns. In certain matrixmaterials the additional filler materials may be provided in one or moresize distributions.

The composite implant can become porous after implantation so as to aidthe resorption process. This porosity can be generated by variousmechanisms including the preferential resorption of filler, such ascalcium sulfate or α-tricalcium phosphate, bioglass or of a polymericcomponent. Alternatively, the formulation can include a biocompatiblesolvent such as DMSO that is leached out of the implant postimplantation. The pores are preferably 100 μm in diameter withinterconnectivity to allow bone ingrowth.

The composite implant may also include an additional porogen. In oneform of the invention, the porogen is sugar or a polysaccharide, such asdextran, but other biocompatible porogens will be apparent to thoseskilled in the art such as crystalline materials in the form of solublesalts.

The porogen may also be in the form of a quickly dissolving fiber withinthe reinforcing element. The fiber may dissolve rapidly, within days forexample, to create a channel for fluid transfer along the intramedullarcanal, increase surface area for more rapid bio-dissolution of theremaining implant, or free up other fillers for timed migration to thelocal environment.

In another embodiment of the present invention, the filler, eitherinorganic or polymeric, may be present in combined amount ranging fromabout 10 to about 50 wt % of the matrix composition. In certain cases itmay be desirable to have the filler content over 50 wt %. If a porogenis added, it will preferably be present in an amount ranging from about15 to about 50 wt %.

Thus it will be seen that the present invention comprises a new approachfor creating high strength mechanical structures for materials withdefined useful life-cycles that will biodegrade or bioabsorb due to thenormal environment envisioned at end of life.

The present invention also provides a new approach for using suchmaterial degradation to provide utility or delivery of a localalteration of the host area (e.g., bodily or environmental) conditions.

Controlling Degradation Rate of Biomedical and Non-Biomedical Devices

It is known that there are materials that can degrade, i.e., reducetheir molecular weight, mass, and/or strength, until the materialdisintegrates into constituent particles or into material with a lowenough molecular weight such that enzymes can digest the remnants. It isalso known that materials can degrade at different rates under differentenvironmental conditions such as temperature, moisture level, and/or pH.However, heretofore, a method has not existed for to control the onsetand rate of degradation under non-ideal material conditions. As anexample, current biodegradable materials are not stiff enough for mostload-bearing applications contemplated herein. The addition of a solubleglass, such as soluble glasses that are made primarily with phosphate,will stiffen the material, increasing the number of applications forwhich the material is suited. However, phosphate glasses are hygroscopicand, therefore, will begin to lose mass from the outside in, losingintimal contact with the surrounding matrix and thus diminishing thebenefits of the composite implant. The application of the layeringtechniques disclosed herein allow for tailoring and controlling theinternal environment in relationship to the external environment so asto increase the shelf life and working life of the composite in order tomake the product practical.

The fibers may be sized with a resorbable metal layer, such asmagnesium, silver, nickel, titanium, and metal alloys such as magnesiumcalcium alloys. Such coatings can be applied via vapor coating,sputtering, atomic layer deposition, chemical vapor deposition, orelectroplating and electroless plating. Other possible coatings caninclude ceramic coatings on the fibers. Such coatings can be made by thesurface reaction of ethyoxysilanes such as tetraethoxysilane,methyltriethoxysilane, dimethyldiethoxysilane, or trimethylethoxysilane;polycarbosilane, or polysilazanes such as perhydropolysilazane- orpolysilizane-modified polyamines.

Another possible approach for sizing utilizes inorganic salts such asmetal phosphates. This approach for sizing is similar to thepretreatment process of metals, wherein acids are used to corrode themetal and thus form metal salt on the surface which delays any furtherdegradation. Typically phosphate salts of iron, calcium, magnesium,zinc, nickel, etc. are used. The sizing can be applied to phosphateglass fibers by immersion in a suitable metal-salt solution which yieldinert phosphate salts that are insoluble in water. This process isself-limiting, as the reaction takes place only as long as phosphateions are released from the glass surface. The reaction can take place ina reactive medium such as an alcohol or glycol. A mixture of salts ispreferred due the formation of smaller crystal size. This process couldalso be combined with an organic pretreatment. This combination ofsalt/organic pretreatment could also act as an adhesion promoter. Afterreaction, the glass fibers can be rinsed and/or vacuum dried. Multipleiterations can be performed with the same compound or different salts.It is also possible to use only a metal phosphate, and diffuse somemetal ions into the glass fiber and obtain a metal clad fiber.

The reinforcement fibers can be cleaned or surface oxidized usingvarious means described in the literature including plasma treatment,corona treatment, ozone treatment, and acidic/basic treatment. Suchtreatments can also be used to introduce specific chemical moieties,such as hydroxyl groups, on the surface of the fibers which can react orprovide improved adhesion with the polymer matrix.

The composite implant can also include fillers that act asself-buffering or degradation-controlling agents. Suitable inorganicbases can be added, such as salts and oxides of alkaline metals,including basic mono-, di-, and tri-phosphates, calcium oxide, calciumhydroxide, magnesium oxide, magnesium hydroxide, calcium phosphate, betatricalcium phosphate, hydroxyapatite, potassium stearate and sodiumstearate. Particles of metals such as magnesium, iron, titanium, andzinc or metal alloys, such as magnesium base alloys, can also be added.Other possible fillers include water-reactive particles, such as calciumoxide or cobalt chloride. Organic bases, such as polyamines, bispidines,and proton sponges, are examples of self-buffering agents. Theself-buffering or degradation controlling agents can be encapsulated ina micro- or nano-capsule, and are released under certain physiologicalconditions.

To control the diffusion rates into and out of the composite implant,the composite implant may be coated with a resorbable metal layer, suchas magnesium, silver, nickel, titanium, and metal alloys such asmagnesium calcium alloys. Such coatings can be applied via vaporcoating, sputtering, atomic layer deposition, chemical vapor deposition,or electroplating and electroless plating. Such metal layers providereduced diffusion, but can also react with water to providebasic/alkaline products that can act as buffering and degradationcontrol agents for the polymer matrix and/or glass fibers.

Another possible approach could be ceramic coatings on the compositeimplant. Such coatings can be made by the surface reaction ofethyoxysilanes such as tetraethoxysilane, methyltriethoxysilane,dimethyldiethoxysilane, or trimethylethoxysilane; polycarbosilane, orpolysilazanes such as perhydropolysilazane- or polysilizane-modifiedpolyamines.

Additional Constructions.

As an example, high modulus polymer pellets can be produced in highvolumes that are used in particulate blasting work to remove oils, rust,paint, etc. This can be especially important for offshore use where thetransport of waste material back to shore is of particular environmentalimportance. The biodegradable particulate may simply be deposited intothe ocean to naturally degrade. It is conceivable that the degradationprocess could yield pH or other shifts in local environment thatprovides a beneficial environment for petroleum-consuming bacterial orenzymes as well.

See Examples 41-60, 75, 79-83.

EXAMPLES Example 1

Preparation of 50/50 prepolymer: 10.60 g polycaprolactone diol (0.02mol), 6.00 g polycaprolactone triol (0.02 mol), both previously vacuumdried and 23.31 mL isophorone diisocyanate (0.10 mol) were stirredcontinuously while heating slowly to 70° C., and then stirred at 70° C.for 2 hours. The heat and stirring was stopped and the reaction wasallowed to sit at room temperature overnight. Yield ˜40 g clear highlyviscous material.

Example 2

Preparation of 60/40 prepolymer: 15.90 g polycaprolactone diol (0.03mol), 6.00 g polycaprolactone triol (0.02 mol), both previously vacuumdried and 27.97 mL isophorone diisocyanate (0.13 mol) were stirredcontinuously while heating slowly to 70° C., and then stirred at 70° C.for 2 hours. The heat and stirring was stopped and the reaction wasallowed to sit at room temperature overnight. Yield ˜50 g clear viscousmaterial.

Example 3

Preparation of hexamethylenediamine aspartic acid ester: 11.62 ghexamethylenediamine (0.10 mol) and 38.86 g tert-butanol was combined,and 34.46 g diethyl maleate (0.20 mol) was added slowly. Reaction was N₂blanketed and heated to 70° C. with stirring for 30 minutes. Reactionwas allowed to sit at room temperature for 120 hours before removingtert-butanol via rotary evaporation at 70° C. and 215-195 mbar. Yield˜45 mL clear slightly viscous liquid.

Example 4

Preparation of isophorone diamine aspartic acid ester: 17.04 gisophorone diamine (0.10 mol) and 38.75 g tert-butanol was combined, and34.43 g diethyl maleate (0.20 mol) was added slowly. Reaction was N₂blanketed and heated to 35° C. with stirring for 15 minutes. Reactionwas allowed to sit at room temperature for 120 hours before removingtert-butanol via rotary evaporation at 70° C. and 215-195 mbar. Yield˜45 mL clear slightly viscous liquid.

Example 5

Preparation of diethylenetriamine aspartic acid ester: 10.33 gdiethylenetriamine (0.10 mol) and 38.74 g tert-butanol was combined, and34.36 g diethyl maleate (0.20 mol) was added slowly. Reaction was N₂blanketed and heated to 35° C. with stirring for 10 minutes. Reactionwas allowed to sit at room temperature for 120 hours before removingtert-butanol via rotary evaporation at 70° C. and 215-195 mbar. Yield˜35 mL pale yellow slightly viscous liquid.

Example 6

Preparation of Polypropylene braid: A Steeger horizontal braider wasused with 0.008″ OD polypropylene monofilament. Braids were run with 24sheath yarns, and the samples that were run with axials had 12 axials,all made of the same 0.008″ OD PP. Samples were run over 5 mm and 10 mmdiameter mandrels.

Example 7

Preparation of Polylactic acid (PLA) braid: A Steeger horizontal braiderwas used with 120d PLLA multifilament. Braids were run with 48 ends, andthe samples that were run with axials had 24 axials, all made of thesame 120d PLLA. Samples were run over 5, 7 and 10 mm diameter mandrels.

Example 8

Preparation of 1.5 mm diameter PLA braid: 1.5 mm braids were constructedaround a core constructed of 90 ends of 75d PLLA, twisted atapproximately 2 TPI. The outer sheath was constructed of 24 ends of 120dPLLA. A Steeger 48 end horizontal braider was used.

Example 9

Preparation of 1.5 mm diameter PLA braid with axial fibers: 1.5 mmbraids were constructed around a core constructed of 90 ends of 75dPLLA, twisted at approximately 2 TPI. The outer sheath was constructedof 24 ends of 120d PLLA, and 12 axial ends of 120d PLLA. A Steeger 48end horizontal braider was used.

Example 10

Preparation of Polyurethane: 2.60 grams of the prepolymer of Example 1was mixed with 0.30 grams of polycaprolactone triol and 0.10 grams ofglycerol at 0.13% w/w dibutyltin dilaurate. The mixture was transferredinto a 3 ml syringe and placed in an oven at 37° C. to cure overnight.The sample was removed from the syringe and cut using a diamond saw tomake a compression test piece. Compression testing showed that thematerial had a compressive stiffness of 1.1 GPa and a yield strength of56 MPa.

Example 11

Preparation of Polyurethane: 2.60 grams of the prepolymer of Example 1was mixed with 1.00 grams of tricalcium phosphate and 0.30 grams ofpolycaprolactone triol and 0.10 grams of glycerol at 0.13% w/wdibutyltin dilaurate. The mixture was transferred into a 3 ml syringeand placed in an oven at 37° C. to cure overnight. The sample wasremoved from the syringe and cut using a diamond saw to make acompression test piece. Compression testing showed that the material hada compressive stiffness of 1.3 GPa and a yield strength of 63 MPa.

Example 12

Preparation of Polyurethane: 2.60 grams of the prepolymer of Example 1was mixed with 2.48 grams of tricalcium phosphate and 0.35 grams ofpolycaprolactone triol and 0.10 grams of glycerol 0.13% w/w dibutyltindilaurate. The mixture was transferred into a 3 ml syringe and placed inan oven at 37° C. to cure overnight. The sample was removed from thesyringe and cut using a diamond saw to make a compression test piece.Compression testing showed that the material had a compressive stiffnessof 1.8 GPa and a yield strength of 71 MPa.

Example 13

Preparation of Polyurethane: 4.05 grams of the prepolymer of Example 2was mixed with 0.50 grams of polycaprolactone triol and 0.15 grams ofglycerol 0.13% w/w dibutyltin dilaurate. The mixture was transferredinto a 3 ml syringe and placed in an oven at 37° C. to cure overnight.The sample was removed from the syringe and cut using a diamond saw tomake a compression test piece. Compression testing showed that thematerial had a compressive stiffness of 1.1 GPa and a yield strength of53 MPa.

Example 14

Preparation of Polyurethane: 4.05 grams of the prepolymer of Example 2was mixed with 2.01 grams of tricalcium phosphate and 0.50 grams ofpolycaprolactone triol and 0.15 grams of glycerol 0.13% w/w dibutyltindilaurate. The mixture was transferred into a 3 ml syringe and placed inan oven at 37° C. to cure overnight. The sample was removed from thesyringe and cut using a diamond saw to make a compression test piece.Compression testing showed that the material had a compressive stiffnessof 1.5 GPa and a yield strength of 69 MPa.

Example 17

Preparation of Polyurethane: 5.26 grams of the prepolymer of Example 1was mixed with 3.81 grams of the aspartic acid ester from Example 5. Themixture was transferred to a 3 ml syringe and placed in an oven at 37°C. to cure overnight. The sample was removed from the syringe and cutusing a diamond saw to make a compression test piece. Compressiontesting showed that the material had a compressive stiffness of 0.6 GPaand a yield strength of 29 MPa.

Example 18

Preparation of Polyurethane: 2.05 grams of the prepolymer of Example 2was mixed with 2.17 grams of the aspartic acid ester from Example 3. Themixture was transferred to a 3 ml syringe and placed in an oven at 37°C. to cure overnight.

Example 19

Preparation of Polyurethane: 2.03 grams of the prepolymer of Example 2was mixed with 2.43 grams of the aspartic acid ester from Example 4. Themixture was transferred to a 3 ml syringe and placed in an oven at 37°C. to cure overnight.

Example 20

Preparation of Polyurethane: 8.10 grams of the prepolymer of Example 2was mixed with 5.70 grams of the aspartic acid ester from Example 5. Themixture was transferred to a 3 ml syringe and placed in an oven at 37°C. to cure overnight. The sample was removed from the syringe and cutusing a diamond saw to make a compression test piece. Compressiontesting showed that the material had a compressive stiffness of 0.7 GPaand a yield strength of 20 MPa.

Example 21

Preparation of high MW DL-lactide: 5.15 grams of DL-lactide monomer wasadded to 0.31 grams ethylene glycol and 0.0016 grams Tin(II)2-ethylhexanoate. Mixture heated to 120° C. for 24 hours. Clear, viscousfluid.

Example 22

Preparation of middle MW DL-lactide: 7.19 grams of DL-lactide monomerwas added to 1.56 grams ethylene glycol and 0.0029 grams Tin(II)2-ethylhexanoate. Mixture heated to 120° C. for 24 hours. Clear,slightly viscous fluid.

Example 23

Preparation of low MW DL-lactide: 7.21 grams of DL-lactide monomer wasadded to 3.10 grams ethylene glycol and 0.0030 grams Tin(II)2-ethylhexanoate. Mixture heated to 120° C. for 24 hours. Clear fluid,very low viscosity.

Example 24

Preparation of Polyurethane: 2.05 grams of prepolymer from Example 2 wasmixed with 0.59 grams DL-lactide from Example 21 and 0.0031 gramsdibutyltin dilaurate. The mixture was transferred to a 3 ml syringe andplaced in an oven at 37° C. to cure overnight.

Example 25

Preparation of Polyurethane: 2.02 grams of prepolymer from Example 2 wasmixed with 0.57 grams DL-lactide from Example 22 and 0.0032 gramsdibutyltin dilaurate. The mixture was transferred to a 3 ml syringe andplaced in an oven at 37° C. to cure overnight.

Example 26

Preparation of Polyurethane: 2.05 grams of prepolymer from Example 2 wasmixed with 0.57 grams DL-lactide from Example 23 and 0.0024 gramsdibutyltin dilaurate. The mixture was transferred to a 3 ml syringe andplaced in an oven at 37° C. to cure overnight.

Example 27

Preparation of Polyurethane with braid reinforcement: One 10 mm IDpolypropylene braid with triaxials was filled with polyurethane fromExample 13. Sample was cured at 37° C. in a cylindrical mold overnight.The sample was removed from the syringe and cut using a diamond saw tomake a compression test piece. Compression testing showed that thematerial had a compressive stiffness of 1.3 GPa and a yield strength of69 MPa.

Example 28

Preparation of Polyurethane with braid reinforcement: Two 10 mm IDpolypropylene braids with triaxials were stacked one inside the otherand filled with polyurethane from Example 13. Sample was cured at 37° C.in a cylindrical mold overnight. The sample was removed from the syringeand cut using a diamond saw to make a compression test piece.Compression testing showed that the material had a compressive stiffnessof 1.0 GPa and a yield strength of 44 MPa.

Example 29

Preparation of Polyurethane with braid reinforcement: Four 10 mm IDpolypropylene braids with triaxials were stacked one inside the otherand filled with polyurethane from Example 13. Sample was cured at 37° C.in a cylindrical mold overnight. The sample was removed from the syringeand cut using a diamond saw to make a compression test piece.Compression testing showed that the material had a compressive stiffnessof 1.3 GPa and a yield strength of 69 MPa.

Example 30

Preparation of Polyurethane with braid reinforcement: Four 10 mm IDpolypropylene braids with triaxials were stacked one inside the other,and three 5 mm ID polypropylene braids with triaxials were stacked inthe same way. The smaller ID braids were placed inside the four 10 mm IDbraids and filled with polyurethane from Example 13. Sample was cured at37° C. in a cylindrical mold overnight. The sample was removed from thesyringe and cut using a diamond saw to make a compression test piece.Compression testing showed that the material had a compressive stiffnessof 1.2 GPa and a yield strength of 63 MPa.

Example 31

Preparation of Polyurethane with braid reinforcement: One 10 mm IDpolypropylene braid with triaxials was filled with polyurethane fromExample 14. Sample was cured at 37° C. in a cylindrical mold overnight.The sample was removed from the syringe and cut using a diamond saw tomake a compression test piece. Compression testing showed that thematerial had a compressive stiffness of 1.0 GPa and a yield strength of53 MPa.

Example 32

Preparation of Polyurethane with braid reinforcement: Two 10 mm IDpolypropylene braids with triaxials were stacked one inside the otherand filled with polyurethane from Example 14. Sample was cured at 37° C.in a cylindrical mold overnight. The sample was removed from the syringeand cut using a diamond saw to make a compression test piece.Compression testing showed that the material had a compressive stiffnessof 1.7 GPa and a yield strength of 75 MPa.

Example 33

Preparation of Polyurethane with braid reinforcement: Four 10 mm IDpolypropylene braids with triaxials were stacked one inside the otherand filled with polyurethane from Example 14. Sample was cured at 37° C.in a cylindrical mold overnight. The sample was removed from the syringeand cut using a diamond saw to make a compression test piece.Compression testing showed that the material had a compressive stiffnessof 2.0 GPa and a yield strength of 66 MPa.

Example 34

Preparation of Polyurethane with braid reinforcement: Four 10 mm IDpolypropylene braids with triaxials were stacked one inside the other,and three 5 mm ID polypropylene braids with triaxials were stacked inthe same way. The smaller ID braids were placed inside the four 10 mm IDbraids and filled with polyurethane from Example 14. Sample was cured at37° C. in a cylindrical mold overnight. The sample was removed from thesyringe and cut using a diamond saw to make a compression test piece.Compression testing showed that the material had a compressive stiffnessof 1.7 GPa and a yield strength of 70 MPa.

Example 35

Preparation of Polyurethane with braid reinforcement: One 1.5 mm ID PLAbraid with axials was loaded into a 2 mm ID tube and filled withpolyurethane from Example 13 that had been degassed with no DBDL. Samplewas cured at 70° C. for two days. The sample was removed from the tubingfor three point bending test.

Example 36

Preparation of Polyurethane with braid reinforcement: One 1.5 mm ID PLAbraid without axials was loaded into a 2 mm ID tube and filled withpolyurethane from Example 13 that had been degassed with no DBDL. Samplewas cured at 70° C. for two days. The sample was removed from the tubingfor three point bending test.

Example 37

Preparation of Polyurethane with braid reinforcement: One 5 mm ID PLAbraid without axials was loaded into a 5 mm ID tube and filled withpolyurethane from Example 13 that had been degassed with no DBDL. Samplewas cured at 70° C. for two days. The sample was removed from the tubingfor three point bending test. Three point bend testing showed that thematerial had a stiffness of 1.2 Gpa and a yield strength of 39 Mpa.

Example 38

Preparation of Polyurethane with braid reinforcement: One 10 mm ID PLAbraid without axials was filled with polyurethane from Example 13 thathad been degassed with no DBDL. Sample was cured at 70° C. in acylindrical mold for two days. The sample was removed from the syringeand cut using a diamond saw to make a compression test piece.Compression testing showed that the material had a compressive stiffnessof 0.8 GPa and a yield strength of 39 MPa.

Example 39

Preparation of Polyurethane with braid reinforcement: One 7 mm ID PLAbraid without axials was placed inside of a 10 mm ID PLA braid withoutaxials and filled with polyurethane from Example 13 that had beendegassed with no DBDL. Sample was cured at 70° C. in a cylindrical moldfor two days. The sample was removed from the syringe and cut using adiamond saw to make a compression test piece. Compression testing showedthat the material had a compressive stiffness of 0.5 GPa and a yieldstrength of 27 MPa.

Example 40

Preparation of Polyurethane with braid reinforcement: One 5 mm ID PLAbraid without axials was placed inside of a 7 mm ID PLA braid withoutaxials and both braids were placed inside of a 10 mm ID PLA braidwithout axials, and the entire stack was filled with polyurethane fromExample 13 that had been degassed with no DBDL. Sample was cured at 70°C. in a cylindrical mold for two days. The sample was removed from thesyringe and cut using a diamond saw to make a compression test piece.Compression testing showed that the material had a compressive stiffnessof 0.8 GPa and a yield strength of 39 MPa.

Examples 41-50 Glass Braid Composites

Preparation of 60/40 prepolymer: 15.90 g polycaprolactone diol (0.03mol), 6.00 g polycaprolactone triol (0.02 mol), both previously vacuumdried and 27.97 ml isophorone diisocyanate (0.13 mol) were stirredcontinuously while heating slowly to 70° C., and then stirred at 70° C.for 2 hours. The heat and stirring was stopped and the reaction wasallowed to sit at room temperature overnight yielding ˜50 g of clearviscous material.

Textile engineered braided glass fibers were prepared having 3 axialfiber bundles bound by bias fiber bundles in a glass content ratio ofapproximately 1:1; the bias bundles were orientated at +/−45 degrees tothe axial bundles; the resulting textile having a predominantlytriangular cross-section. A single braid approximately 1.9-2 mm indiameter and about 80 mm in length was placed in a PTFE tube and aselection of polyurethane formulations in the table below were injecteddown the tube using both injection pressure and vacuum suction toproduce substantially void free constructions with approximately 50%eglass by volume. The constructions were cured at 70 degrees C. in atight fitting stainless steel tube and cut from the PTFE tube. The curedcomposite pins were removed and subjected to mechanical testing. Duringthe same operation PTFE tubes without braid reinforcements were likewiseprepared so comparisons in mechanical properties of the unfilled andglass reinforced structures could be made.

Examples 41-50 use commercially available polyester polyols from KingIndustries (Kflex series), Perstorp (Capa) and Invista (Terin), all areknown to hydrolytically breakdown over a period of time under ambientaqueous environments. The isocyanate prepolymer was the same asdescribed in Example 2 with the polycaprolactone diol and triol beingsourced from Perstorp. The polyols were precombined and allowed to standto remove an air entrainment. The prepolymer described above wascombined with the prepolymer blend at the ratios shown in the tablewhich were calculated from hydroxyl value and isocyanate valuecontributions to provide stoichiometric cure. The mixture was degassedbefore injecting into the tubes to avoid air entrainment. The sampleswere cured at 70 degrees C. for 48 hours and then conditioned underambient conditions before being tested for flexural strength.

Examples 41 42 43 44 45 46 47 48 49 50 Polyol Kflex 366 60 60 Kflex 30760 60 Kflex XM 60 60 337 Kflex 148 60 60 Terin 168G 60 60 Capa 4101 3030 30 30 30 Capa 4800 30 30 30 30 30 Glycerol + 10 10 10 10 10 10 10 1010 10 10% DBTL Total 100 100 100 100 100 100 100 100 100 100 Isocyanate256 210 243 221 220 173 211 184 245 208 prepolymer Gel time 13 18 11 1719 10 8 18 20 27 (min) rt Cured 1.4 0.8 1.9 0.7 2.0 1.6 2.3 1.6 1.5 2.2Resin Flex ductile ductile ductile ductile ductile ductile ductileductile ductile ductile Modulus (GPa)/ Failure Mode Cured 15.6 12.9 20.316.2 18.1 16.4 16.6 11.7 17.3 14.8 Composite ductile slip break slipslip ductile break ductile ductile Ductile Flex Modulus (GPa)/ Failuremode

The data in the table above shows the effect of the polyol type andcomposition on cure time and flexural modulus of the cured resin and theability to tailor performance. Similarly the incorporation of the glassreinforcement showed substantial increases in flexural modulus by 10 to15 fold in most cases still maintaining a ductile failure mode. Thisincrease is substantially higher than the change in properties seen inprior examples with polypropylene and PLA fiber reinforcements.

Examples 51-60

Using the same procedure as described in Examples 41-50 a series ofcured polyurethane compositions were tested for mechanical strengthagainst glass filled composites using the E glass braid structure alsodescribed in Examples 41-50.

Examples 51 52 53 54 55 56 57 58 59 60 Polyol Capa 2504 45 35 30 35 3045 35 30 35 30 EG/Dilactide (1:2 45 35 30 35 30 Molar Ratio)EG/Dilactide (1:4 45 35 30 35 30 Molar Ratio) Capa 4101 0 20 30 0 20 30Capa 4800 20 30 20 30 Glycerol + 10% 10 10 10 10 10 10 10 10 10 10 DBTLTotal 100 100 100 100 100 100 100 100 100 100 Isocyanate 230 233 234 209196 205 213 217 189 180 prepolymer Gel time (min) 81 96 124 124 88 32 3422 34 22 rt Cured Resin Flex 2.9 2.4 1.3 1.6 1.3 2.6 2.3 2.6 2.5 1.5Modulus (Gpa)/ ductile ductile ductile ductile ductile ductile ductileductile ductile ductile Failure Mode Cured Composite 23.6 17.3 18.0 14.916.7 15.5 13.4 15.8 8.2 2.8 Flex Modulus ductile slip break slip slipductile break ductile ductile Ductile (GPa)/ Failure mode

Examples 51-60 show the effect of a different type of polyester polyol,in this case made from the reaction of ethylene glycol and DL dilactideusing the method below:

Preparation of high MW DL-lactide: 5.15 grams of DL-lactide monomer wasadded to 0.31 grams ethylene glycol and 0.0016 grams stannous2-ethylhexanoate and heated to 120° C. for 24 hours producing a clearviscous fluid.

Preparation of DL-lactide diol: 7.19 grams of DL-lactide monomer wasadded to 1.56 grams ethylene glycol and 0.0029 grams stannous2-ethylhexanoate. Mixture heated to 120° C. for 24 hours producing aclear slightly viscous fluid.

Preparation of low DL-lactide diol: 7.21 grams of DL-lactide monomer wasadded to 3.10 grams ethylene glycol and 0.0030 grams stannous2-ethylhexanoate. Mixture heated to 120° C. for 24 hours producing aclear low viscosity fluid.

By selecting the type of dilactide polyol and also the amount, theflexural modulus of the cured resin may be changed from 1.3 GPa to 2.9GPa which is very significant.

In addition, as with Examples 41-50, the flexural modulus of the glassfilled composites may be change from 2.8 GPa to 23.6 GPa thusdemonstrating the ability to tailor the physical properties of theimplant material.

Example 61

A Polyurethane was prepared: 4.05 grams of the prepolymer of Examples41-50 was mixed with 2.01 grams of tricalcium phosphate and 0.50 gramsof polycaprolactone triol and 0.15 grams of glycerol 0.13% w/wdibutyltin dilaurate. 3 mm proximal entry holes and 3 mm mid-shaftlesions were created in 5 New Zealand White rabbits. A braided constructwas compressed into a sheath and delivered through a catheter with aninner diameter of approximately 0.080 inch. The braided construct wasinserted though the proximal entry and positioned across the mid-shaftlesion. The 60/40 matrix mixture from above was injected within andaround the construct using a catheter with a distal portal. There wassignificant foaming due to the contact of the matrix with the water inthe blood that obscured the procedure. The matrix cured in situ andformed an internal composite splint, however in some instances thematrix expanded and/or flowed into the fracture gap. After 6 weeks,lesions demonstrated healing except where the matrix had entered thefracture gap. In all cases, no abnormal bony reactions or infectionsoccurred. This demonstrates that a modular splint can be constructedthrough a minimally invasive entry and will not interfere with normalbone healing using an engineered matrix reinforcement filled in serieswith a matrix material. It also highlights the requirement for acontainment system to maintain the fracture gap as well as contain thecuring of the polymer and direct expansion of the matrix.

Example 62

Soluble phosphate glass fibers were incorporated into a compositestructure similar to those from Examples 41-50 by placing a bundle ofsized strands approximately 1.9-2 mm in diameter and about 80 mm inlength in a PTFE tube and injecting the degassed mixture of pre-polymersfrom Example 51 down the tube using both injection pressure and vacuumsuction over many hours to produce predominantly void free compositeswhich were cured at 70° C. The PTFE tube was cut and the cured pinsremoved and subjected to mechanical testing. A flexural modulus of 37GPa was produced from the pins with further analysis demonstrating a 71%fiber volume in the sample. This demonstrates that the use of abioresorbable glass as the reinforcements from this invention producesresults similar to the aforementioned e-glass samples and that theinvention can produce composites with greater than bone-like physicalproperties. It also demonstrated the long length of time required tofill and wet-out non-textile engineered uniaxial directed bundles withhigh fiber volume.

Example 63

Glass fibers were procured from AGY (60 fbr glass above) and PPG (30 fbrglass above). Each glass fiber had different fiber diameters. These werecompared to two types of Bio-soluble glasses axially orientated within acomposite using the same polyurethane matrix from Example 51 using thesame methods as described in Example 62. A comparison of flexuralmodulus is shown in FIG. 30 and demonstrates that the smaller “60 fiber”glass (when adjusted for fiber volume) is a good surrogate forbio-soluble glass fibers and therefore justifies the use in Examples41-60 and those that follow.

Example 64

Glass fibers were procured from AGY (60 fbr glass above) and PPG (30 fbrglass above) and used as axial reinforcing elements in composite 2 mmpins using the same polyurethane matrix and method of constructiondescribed in Example 63. The fibers differed in two manners, thediameter of one fiber was twice that to the other (filament diameterswere the same for both) however the fiber volume was kept consistent,and there was a coating difference between the two (proprietary to eache-glass manufacturer). A comparison of flexural modulus is shown in FIG.30 with a marked difference in modulus between the two composite rods.The results demonstrate that the axial strength may be dramaticallyincreased by through the use of an appropriate fiber coating used tocompatibalize the matrix to the reinforcing elements.

Example 65

Textile E glass braids were prepared having 6 axial fiber bundles(predominantly circular cross-section) bound by bias fiber bundles in aglass content ratio of approximately 1:1 axial to bias fiber volume; inone sample the bias bundles were orientated at +/−45° to the axialbundles, in the other sample the bias bundles were orientated at +/−30°to the axial bundles. 2 mm composite pins were built using the samepolyurethane matrix and method of construction described in Example 63.The flexural modulus of each are compared in FIG. 31 demonstrating thatthe axial contribution to structure in this invention can be increasedsignificantly by changing the bias angle within the braided reinforcingelements.

Example 66

Textile glass braids were prepared having either 6 axial fiber bundles(predominantly circular cross-section) or 3 axial fiber bundles(predominantly circular cross-section) bound by bias fiber bundlesorientated at +/−45° to the axial bundles in a glass content ratio ofapproximately 1:1 axial to bias fiber volume and designed to contain thesame volume of fiber per unit length. 2 mm composite pins were builtusing the same polyurethane matrix and method of construction describedin Example 63. The flexural modulus of each were compared in FIG. 32,demonstrating no significant difference. Thus, the shape of a singlereinforcing element will not alter its ability to reinforce a matrix.

Example 67

Textile glass braids were prepared having 6 axial fiber bundles bound bybias fiber bundles in a glass content ratio of approximately 1:1; thebias bundles were orientated at +/−45 degrees to the axial bundles; theresulting textile having a predominantly circular cross-section. Thefiber by weight per unit length braid was designed to be approximatelythe same as the predominantly triangular cross-section E glass braidsfrom Examples 41-50. Multiple sections of this braid and that fromExamples 41-50 were fit into a PTFE tube with an inner diameter ofapproximately 7.5 mm. While making three samples using each braid type,12 of the predominantly triangular cross-section braids could fitparallel in the PTFE tube (final FV 49.4%) while only 11 of thepredominantly circular cross-section braids could fit (FV 47.0%). Thisconfirms the importance of shape to reinforcement element nesting andtherefore final implant fiber volume. The concept of nesting and fit isdemonstrated in FIG. 33.

Example 68

The measures of flexural modulus for Example 67 showed no significantdifference despite the inclusion of more reinforcement rods into thecomposite. The large number of reinforcement rods makes the differencein mechanical properties small, so the ratio of standard deviation toaverage value (expressed in %) is used to compare the variability. Thetriangular vs. circular cross section braids come off of themanufacturing storage roll differently. The triangular braids maintain ashape, while the circular ones come off of the roll in a rectangularshape. The rectangular shape acts to promote intra-braid nesting,creating good axially oriented columns (better bending). The variabilityin bending performance slightly favors the rectangle/circular design (5%vs. 9% variability). However, in torsion, the triangular shapes are muchless variable than the rectangular/circular (2% vs. 13%). Showing thatin torsional resistance, the triangular shapes inter-nest much better(see FIG. 34).

The shapes are also important in function. The long triangular shapeshold a vertical posture better in a less hardened, more flexible(non-composite) state, therefore will be better for insertion into longstraight bones such as the humerus, tibia or femur. The rectangularshapes bend better around curves in bones such as the clavical withoutbuckling.

Example 69

The value of the braided reinforcement construct is further demonstratedwhen compared to uni-axial constructs. Uni-axial constructs were madewith the same fibers using the same methods as those in Example 67 insimilar fiber volumes (45% FV vs. 49.4% FV—triangular constructs and 47%FV for circular constructs). The performance in bending was better thanthe braids (all fibers are axially oriented), however the results hadsignificantly higher variability (17% compared to 5 or 9%) and took muchlonger to fill with resin and had spots within the construct that werenot completely wet-out after hours of filling. In torsion, the uni-axialcomposite variability was similar (7% compared to 2%, triangularconstructs or 13% circular constructs) but the performance was 29% lowerthan the braided constructs. This performance is expected is expectedsince the braided constructs (both circular and triangular) have 50% ofthe fiber volume contributing 50% of its strength (45° bias angles) tonon-axial forces. This is an example of reduced filling variabilityusing braided constructs due to the engineering in of hydrostatic forceinducing elements that pull matrix through the full construct. It alsodemonstrates the advantage of being able to variably assignreinforcement to different directions of support. In addition, theconstructs are simple, loadable structures, wherein uni-axial constructswould be very difficult to load without significant coating (that wouldreduce wet-out and/or fiber volume) to stiffen the components.

Example 70

An example is depicted in FIG. 35 of how multiple triangularreinforcement shapes such as those depicted in Example 68 can becombined, in pre-cured or thermoplastic molding processes, to createpins of different shapes as well. Three of the triangular reinforcementconstructs from Example 68 can be combined to create a well nested finalimplant of unique shapes

Example 71

FIG. 36 shows how the number, size and orientation of axial fibers couldbe combined within a thermoplastic, reaction injection molding, orpultrusion/extrusion technique to form different shapes including longcontinuous shapes and a canulated form for direct implants or as part ofthe in situ curing method described within this invention. The formspresented in Example 68 are readily applicable to some of the shapesshown in FIG. 36.

Example 72

PCL/PLA copolymer thermoplastic (Capa 8502A) was compounded withbiodegradable glass (Mo-Sci Corp GL0122P/-53) and assessed formechanical properties. Biodegradable glass was blended intothermoplastic at 5% glass volume and 25% glass volumes. Blends weremolded into cubes (roughly 1 cm×1 cm×1 cm) and tested for compressivemodulus. 5% glass volume cubes resulted in a 10% improvement in elasticmodulus as compared to control cube of thermoplastic without glass. 25%glass volume cube resulted in a 68% improvement in elastic modulus ascompared to control cube of thermoplastic without glass. The results areshown in FIG. 37.

Example 73

An FEA model was created to judge the requirements of an intra-medullarsplint. The model was loaded with a 300N force at the proximal end ofthe bone (shoulder joint) and kept locked at the distal (elbow) end. Thewhole bone displacement at the proximal end of the bone was measuredunder unbroken, a partial proximal humeral fracture (a model of afracture half-way through the bone) and while splinted with anintra-medullar splint with increasing step values of Young's modulus inthe partial and full fracture bone. The results demonstrated that asplint with a Young's modulus of greater than 12 GPa was necessary toreturn the bone to its unbroken performance level.

Example 74

A bone break model was created with a composite tube (Garulite) with an8.10 mm ID to empirically support the FEA model from Example 73. Nine 75mm long flexible braided glass reinforcement rods as described inExamples 41-50 (between 30-40% FV) were loaded into a 10 mm diameter PETballoon through a tube that could only accept the rods one at a time.The bag and rods were positioned across an incomplete cut in the tube(approximately 0.7 mm in distance) and filled under vacuum from a singlemanually extended 60 cc syringe with the polyurethane from Example 51then cured at 70° C. The tube break was tested pre and post splintpositioning in non-destructive and destructive 4 point bend testing. Innon-destructive testing, the load needed to cause strain at the fractureline of 0.5% increased from 28 N to 260 N. In destructive testing, therepair withstood 516 N prior to reaching 2% strain and yielded at about3.5% strain at 800 N of loading with a peak load of 880 N and anon-catastrophic failure mode. Since bone typically breaks at 1.5-2%strain and will experience secondary bone healing between 2-10% strain,this example demonstrates that this invention, with a reasonable finalfiber volume will increase the stiffness of a fractured tubular bone toa degree that it approaches the performance criteria of bone and willallow secondary healing to occur.

Example 75

Thermoplastic P4HB beads and PLA beads as received were mixed withphosphate based soluble glasses and incubated in phosphate based buffersolution at 50° C. for 52 days in vials, 50/50 by weight. Buffer waschanged periodically as pH shifted. Beads were dried thoroughly after 52days and analyzed via GPC. For P4HB, the higher molecular weight portion(Mz) decreased significantly regardless of additive. Lower molecularweight portion (Mn) increased slightly more in control than in sampleswith additives. Addition of 1 glass type effected on speed ofdegradation for both high molecular weight portion (Mz) as well as lowermolecular weight portion (Mn) of samples. For PLA, there was a largedecrease in MW regardless of additive. Soluble glass 1 very slightlyslows degradation while soluble glass 2 speeds it up. This exampledemonstrates that a thermoplastic, soluble glass composite degrades.Additionally, P4HB—known to degrade primarily by enzymaticdegradation—was demonstrated to have increased hydrolytic degradationdue to the addition of soluble glass.

Example 76

2 mm pins were constructed as per Example 62 with the polyurethane ofExample 51 and phosphate based soluble glass uni-axial fibers. The pinswere coated with a well established material that retards the ingress ofwater to a rate of 1 gram*mil/(100 in²)*day. The loss of stiffness wasseverely retarded over a 25 day period with a stiffness that remainedwell above the need expected in the FEA analysis from Example 73. Thisdemonstrates that the use of an external barrier such as hydrophobicproperties of the bag/balloon or an external coating on a pre-formedstructure will serve to retard the degradation process of the fullimplant. See FIG. 38.

Example 77

The time it takes to fill a multi-braid structure was measured. Avolumetric model was created with an increasing number of triangularbraids (as per Examples 41-50) loaded horizontally. A polyurethane asper Example 51 (viscosity approximately 1000 cp) was filled under vacuumalone (no added positive mechanical pressure from the injection syringe)provided by a fully extended 60 cc syringe. The injection time wastracked along with the volume injected. The results are shown below (thefit lines are for visualization only, not a mathematical fit) for thehighest fiber volume (# of braids) loaded per model size (described bymodel diameter). The models all had different overall volumes to fillbut the same length (i.e., distance from bottom of model to top; the twolargest models had approximately 61% fiber volumes to wet-out and thesmallest model was a slightly higher fiber volume of 68% to fill. Thefill and wet-out was completed in 90 seconds or less for the two largestvolumes and took about 2 minutes for an “over-stuffed” small model. Thisdemonstrates a reasonable fill time for in situ filling in an operativeenvironment for building a splint. There were occasions when thereinforcing rods were too close to the inflow of the resin, thisrepresents instances where the rod insertion could have kinked orblocked the inflow channels. These instances severely retarded inflowand reinforce the importance of relatively robust (but flexible)reinforcement rods. It also highlights the importance and addition ofvacuum alone, from a simple disposable device (e.g., a syringe). SeeFIG. 39.

Example 78

Textile E glass braids were prepared having either 6 axial fiber bundles(predominantly circular cross-section) or 3 axial fiber bundles(predominantly circular cross-section) bound by bias fiber bundlesorientated at +/−45° to the axial bundles in a glass content ratio ofapproximately 1:1 axial to bias fiber volume and designed to contain thesame volume of fiber per unit length. 2 mm composite pins were builtusing the same polyurethane matrix and method of construction describedin Examples 41-50. The flexural modulus of each are compared in FIG. 41demonstrating no significant difference. Thus, the shape of a singlereinforcing element will not alter its ability to reinforce a matrix.

Example 79

Polyurethane matrix was combined with phosphate based soluble glassfibers to produce material pins as per Example 62. The pins weredegraded in a buffer solution at 70° C. to accelerate degradationeffects. The remaining weight compared to the starting level of solubleglass material was found to correlate with the degradation rate in anon-linear fashion as shown in FIG. 42, thus demonstrating control ofdegradation rate of the product.

Example 80

Thermoplastic PLA polymer was co-mingled with different types ofphosphate based soluble glass fibers and submerged in a 7.4 pH buffersolution with periodic refreshes of the solution. FIG. 43 shows theresulting change in local environmental pH between PLA alone and PLAcomingled with 2 different types of soluble glass fibers, each giving adifferent resulting environment.

Example 81

Thermoplastic Polyurethane polymer was co-mingled with different typesof phosphate based soluble glass fibers and submerged in a 7.4 pH buffersolution with periodic refreshes of the solution. FIG. 44 shows theresulting change in local environmental pH between PLA alone and PLAcomingled with 2 different types of soluble glass fibers, each giving adifferent resulting environment. Thus demonstrating the ability tomodify the local environment during or after material degradation.

Example 82

The novel composite structure can be used to form various biodegradabledevices, e.g., the biodegradable screw shown in FIG. 45. In this form ofthe invention, a mold, having a cavity which is the shape of a screw, isfilled with the matrix material and the reinforcing elements, e.g., bypositioning the reinforcing elements (e.g., woven fibers) in the moldcavity and flowing the matrix material around the reinforcing elements.Then the composite structure is cured in the mold and removed as aformed article ready for use. Alternatively, the reinforcing elements(e.g., nanoscale fibers) may be mixed with the flowable matrix materialand the mixture flowed into the mold cavity for molding and curing.

Example 83

In another example, the novel structure can be used to form abiodegradable syringe. More particularly, and looking now at FIG. 46,there is shown a syringe system comprising a reservoir of known, wellmetered volume having a distal injection end and an open end accepting aplunger, contiguously tipped with a low modulus material capable offorming a movable hydrostatic seal with the sides of the reservoir andthe plunger having a length enabling single handed actuation. The distalend of the reservoir forms a nozzle that enables a range of injectionfluid viscosities and providing a needle sharp enough to penetratedermus and musculature and strong enough to resist breakage withreasonable use.

Each of the components described above can be constructed of variouscomposites that are created from at least one reinforcing elementembedded within a matrix. In a preferred embodiment of the invention,the syringe reservoir is created with a biodegradable thermoplasticmaterial embedded with soluble glass particulate and imparted withhydrophobicity on the internal surface. The hydrophobic surface allowsfor the storage of pre-filled injectable material for a predictable timeframe. The soluble glass has an autocatalytic water initiatedrelationship with the thermoplastic such that a cascading change in pHaccelerates biodegradation in a composting environment.

In a preferred embodiment, and referring to FIG. 46, the plunger isconstructed of two different parts, one part is a thermoplastic materialas described above. The other part is a thermoset or thermoplastic ofsimilar design but having a functional modulus much closer to that ofrubber. Soluble glass particulate completes the composite given anautocatalytic water initiated relationship with the thermoplastic suchthat a cascading change in pH accelerates biodegradation in a compostingenvironment.

In a preferred embodiment of this invention, and referring to FIGS. 46and 2, the needle is of separate construction with a fitted proximal endor with the capability to be attached to the reservoir via adhesion,energy induced welding (RF welding or the like), or some other suchmeans. The needle is constructed of a thermoset or thermoplastic encasedcircular braid of a high modulus reinforcing element such as solubleglass, FIG. 47. The reinforcing element serves to enhance the needle(s)resistance to axial and bending forces and acts as a biodegradationinitiator and/or auto-catalyzing agent enabling practicable composting.

Examples Of Barriers Used In Biodegradable High Strength CompositeSystems Example 84

2 mm diameter round pins (5 cm) long were made out of a biodegradablecomposite like example 62 in Ortho040506. One group of pins was coatedwith a non-degradable well established and measurable (WVP−1 g*mil/100in² day=0.4 g*mm/m² day)) substance to a thickness of 0.5 mil (13 μm), acontrol group remained uncoated. The groups of pins were submerged indistilled water at room temperature (20° C.). The loss of mechanicalproperties (bending stiffness) was measured periodically. The rate ofstiffness loss was reduced from 16% per day to 1.1% per day with thecoating.

Example 85-89

A fully degradable pin with dimension from above can be reduced topractice using a number of available barrier substances described inliterature as listed in the table below (all at temperatures between 20and 25° C.):

WVP Req (g mm/m²* Thickness Example Material day) (μm) Ref 85 20 μmthick commercial Poly 1.1  44 [1] (Lactic Acid) Film 86 Al₂O₃ Coated PLAfilm 0.7  21 [1] 87 Poly Hydroxybuterate-co- 0.3  11 [2] valerate (6%valerate) 88 Poly (Lactic Acid) 66% 2.1  66 [2] Crystallinity 89 Polyε-capralactone 4.4 143 [2]This table shows that results similar to that above can be achieved withsubstances considered biodegradable or bioabsorbable with a singlebarrier layer between 0.8 and 11 times the thickness of the material inexample 1 above.

Example 90-93

For the examples above, the temperatures studied were approximately20-25° C. If the pin were to be designed for use inside of a body, as asmall bone splint for example, then the temperature would be 37° C.,resulting in more rapid diffusion of water (Brownian motion). A fullydegradable pin with dimension from Example 1 above can still be reducedto practice with a variation of the thickness (calculated using anestimate of the Arrhenius equation):

WVP Req (g mm/m²* Thickness Example Material day) (μm) Ref 90 20 μmthick commercial Poly  3.0  96 calculated (Lactic Acid) Film 91 PolyHydroxybuterate-co-  0.8  25 valerate (6% valerate) 92 Poly (LacticAcid) 66%  4.9 159 Crystallinity 93 Poly ε-capralactone (PCL) 10.6 343This table shows that results similar to Example 84 can be achieved withsubstances considered biodegradable or bioabsorbable with a singlebarrier layer between 2 and 27 times the thickness of the material inExample 84 above.

Example 94

The thicknesses of the coatings in Examples 90-93 are high for some ofthe more readily available and acceptable materials for humanimplantation. In addition there may be a desire to exact a compliantdevice, such as an implantable medical balloon. Therefore, the thicknessof the barrier would need to stay within the range of a compliantmaterial. To exact this, an insoluble solid suspension is added to thepolymer to reduce the permeability rate. It has been reported thatamounts as small as 5 wt % of clay added to polymer can halve thepermeability [3]. In the same publication, the effect on permeabilityrises exponentially for up to 20 wt % of additive. To reduce this topractice, the PCL from Example 93 above is compounded with 10 wt %biocompatible insoluble such as Mg(OH)₂— which has a plate-likemorphology after undergoing a specific heating profile. Mg(OH)₂ isestimated to be half as effective as clays, therefore the effect is toreduce the WVP of the material from 10.6 to 5.3 g mm/m²*day. With thismaterial the required barrier thickness is reduced from 343 to 171 μm(≈0.006″). Given the inherent flexibility of PCL, this is a goodthickness for a compliant human implantable degradable balloon.

Example 95

An alternate example (to Example 109) of a barrier appropriate for useas a compliant human implantable degradable balloon is enacted by theuse of multiple co-extruded layers of polymers. The calculated WVTR ofthe resulting films of examples 1-4 is 31 g/m²*day. To enact a thinnerdesign with biologic benefits layers of a balloon can be created byco-extrusion of a tube and subsequent expansion using balloon formingmethods. Other methods such as dip coating can also be used. Theresulting WVTR is calculated using a parallel network equation. [4]

WVP WVTR (g mm/m²* Thickness (g/m²* Layer Material day) (μm) day) OutPoly (Lactic Acid) 66% Crystallinity/ 4.9  25.4 193 HydroxyapatiteSuspension Middle Poly ε-capralactone (PCL)/ 5.3* 25.4 209 Mg (OH)₂ 10wt % suspension Inside Poly (Lactic Acid) 66% Crystallinity/ 2.5* 50.8 48 Mg (OH)₂ 10 wt % suspension *Estimated halved WVP due to insolublecomponents at 10 wt % 100    33This example shows that by layering three dissimilar materials withdifferent water transfer rates, a barrier with similar waterpermeability as those of examples 1 through 4 (33 g/m²*day vs. 31g/m²*day) with a relatively thin material (100 μm, 0.004″). In addition,the material has an outer coating infused with Hydroxyapatite which isadvantageous if implanted near bone, and the compliance and adhesivecapability of the middle layer of PCL gives some resilience to theoverall structure.

REFERENCES FOR EXAMPLES 84-95

-   [1] T. Hirvikorpi, M. Vähä-Nissi, A. Harlin, M. Salomäki, S.    Areva, J. T. Korhonen, and M. Karppinen, “Enhanced water vapor    barrier properties for biopolymer films by polyelectrolyte    multilayer and atomic layer deposited Al2O3 double-coating,” Appl.    Surf Sci., vol. 257, no. 22, pp. 9451-9454, September 2011.-   [2] R. Shogren, “Water vapor permeability of biodegradable    polymers,” J. Environ. Polym. Degrad., vol. 5, no. 2, pp. 91-95,    1997.-   [3] J.-W. Rhim, H.-M. Park, and C.-S. Ha, “Bio-nanocomposites for    food packaging applications,” Prog. Polym. Sci., vol. 38, no. 10-11,    pp. 1629-1652, October 2013.-   [4] K. Cooksey, “Interaction of food and packaging contents,”    Intell. Act. Packag. Fruits Veg., pp. 201-237, 2007.

Example 96

A two component polyurethane matrix material was made by preparing(component A) polyol blend consisting of a polycaprolactone triol (70%by weight), 1,4;3,6-dianhydrous-d-sorbitol (15%), and a citric acidester (15%). The polyol was mixed and crosslinked with a hexamethylenediisocyanate trimer (component B) to provide a polyurethane matrix thatis used in the application to bind reinforcement fibers to ultimatelyform a composite. The isocyanate (NCO)/hydroxyl (OH) stoichiometry ratiowas 1.1. Catalyst was added to polyisocyanate to catalyze theisocyananate-hydroxyl reaction which forms the polyurethane. Catalystselection was based on compatibility and stability in the system. Inthese studies, a zirconium catalyst was added to the isocyanate prior tomixing the polyol and isocyanate components.

Viscosity.

Viscosity for this application is important for the injection process ofexiting the syringe, flowing through a static mixer (to mix components Aand B), through the catheter, into the implant enclosure which containsreinforcing fibers. Proper viscosity is also critical such that thereinforcing fibers become completely “wet out” by polyurethane beforegelling begins. centipoise, respectively. Similar viscosities ofcomponents A and B is critical to provide efficient and thorough mixingof the 2 components. The viscosity of the mixed components A and B oneminute after mixing was 1440 cps.

Exotherm.

Proper curing of the polyol-isocyanate reaction to form the polyurethanedescribed above causes an exotherm and results in development ofcritical mechanical properties. The reaction rate and the extent ofexotherm can be controlled by altering amount of catalyst used, and byamount of reinforcement. Preparing a 5 gram sample of polyurethane with0.17% zirconium catalyst resulted in a maximum temperature of 35° C.twenty four minutes after mixing. Increasing the zirconium catalystlevel to 0.3% resulted in a maximum temperature of 53° C. twelve minutesafter mixing. The final matrix glass transition temperature was 46° C.with each of catalyst levels tested.

With 30% volume fiber reinforcement and 70% polyurethane matrix, and0.17% zirconium catalyst, the maximum temperature of 24° C. occurs overa time frame of 10 to 20 minutes after mixing. This compositecomposition with 0.3% catalyst causes a maximum temperature of 33° C.twelve minutes after mixing.

Pot Life.

As with exotherm, pot life can be controlled by varying amount ofcatalyst used in polyurethane. The polyurethane for this procedure has ausable working/application time (also known as potlife) in which it canbe efficiently injected to wet out reinforcement fiber within theimplant enclosure. An acceptable viscosity range has been observed to beroughly 500 cps-5000 cps. The useable working time (viscosity of mixedcomponents A and B reaching 5000 cps) with 0.3% zirconium catalyst wassix minutes. The working time of this same system with 0.2% zirconiumcatalyst was eleven minutes.

Mechanical Strength.

Mechanical strength development is very important for implantperformance, as it determines when the patient can be moved out of theoperating room, and when the patient can support him or herself. Acomposition containing 50% (by volume) of the above polyurethane with0.2% zirconium catalyst and 50% by volume glass fibers was prepared intospecimens for flexural modulus testing. After 6 days curing at 37° C.the flexural modulus was 12 GPa.

Example 97

A polymer matrix consisting of both caprolactone and lactic acid groupswas formulated. Component A of the polymer matrix consisted of apoly(caprolactone) triol (70% by weight), poly(caprolactone-co-lactide)triol (10% by weight), 1,4;3,6-dianhydrous-d-sorbitol (15%), and acitric acid ester (5%), plus a bismuth catalyst (0.09% by weight). Thepolyol (component A) was mixed and crosslinked with a hexamethylenediisocyanate trimer (component B) to provide a polyurethane matrix thatis used in the application to bind reinforcement fibers so as to,ultimately, form a composite implant. The isocyanate (NCO)/hydroxyl (OH)stoichiometry ratio was 1.1. Viscosity of components A and B were 1210and 1066 cPs, respectively. The pot life of the formulation is around 4minutes. The maximum temperature reached is 65° C.; however, in thepresence of 40% fiber volume, the maximum temperature reached is 45° C.

Example 98

Round pre-cured pins for intramedullary (IM) bone fixation with a 2 mmdiameter and 3 cm long, were made out of a biodegradable composite,consisting of glass braid reinforcement, a polymer matrix, and an outerbarrier. The glass braids were made out phosphate glass fibers with 3axial fiber bundles (predominantly circular cross-section) bound by biasfiber bundles orientated at +1-45° to the axial bundles. Component A ofthe polymer matrix consisted of a poly(caprolactone-lactic acid) triol(80% by weight), 1,4;3,6-dianhydrous-d-sorbitol (15%), and a citric acidester (5%), plus a tin catalyst (0.13% by weight). The polyol was mixedand crosslinked with a hexamethylene diisocyanate trimer (component B),mixed with 15% hydroxyapatite, to provide a polyurethane matrix that isused in the application to bind reinforcement fibers to, ultimately,form a composite implant. The isocyanate (NCO)/hydroxyl (OH)stoichiometry ratio was 1.1. Hydroxyapatite is added to the polymermatrix as it is biocompatible, osteoinductive, and acts as degradationcontrol buffer. The two parts (components A and B) are mixed in a ratioof 1:2, and reacted with the glass reinforcement (55% fiber volume) withthe help of a tin catalyst at a concentration of 0.13%, and cured at 70°C. overnight. The cured rods are coated with a 100 micron thick layer(i.e., a coating) that consists of an inner barrier layer and an outercompatibilizer layer. The inner barrier layer is a 75 micron thick waterbarrier layer, and consists of high aspect ratio magnesium hydroxidemicroparticles (average size 10 micron diameter and 200 nm thick),dispersed in a degradable polyester polyurethane matrix. The outercompatibilizer layer consists of beta tricalcium phosphate, dispersed ina degradable polyester polyurethane matrix. To increase the adhesion ofthe coating to the pins, the pins are slightly roughened/structured. Thecoating has a water vapor permeability (WVP) of 2 g*mil/100 in² day (0.8g*mm/m² day). Where the pins are used for hammer toe fixation, the curedpins are cut to the desired size, typically ranging from 2-3 cm.Similarly-formed pins, of appropriate size, can be used for other typesof IM fixations, including small bones, clavicle, ribs, radius, ulna,etc.

Example 99

Pins are formed as in Example 98, except that one or both the ends ofthe pins are tapped and/or barbed for securing the pins to bone.

Example 100

This example is for pre-cured rods for fixation of tibia, femur, andhumerus. Round rods with 12.5 mm diameter, and 30 cm long, were made outof a biodegradable composite, consisting of glass braid reinforcement, apolymer matrix, and an outer barrier. The glass braids were made outphosphate glass 6 axial fiber bundles (predominantly circularcross-section) bound by bias fiber bundles orientated at +/−45° to theaxial bundles. The polymer matrix was apoly(caprolactone-co-lactic-co-glycolide) polyurethane system, andconsisted of a mixture of two parts. The first part (Part A) consists ofa polyester polyol mixture with a catalyst, whereas the second part(Part B) consists of isocyanate prepolymer with 25% betatricalciumphosphate, which is biocompatible, osteoinductive, and acts asbuffer control. The isocyanate (NCO)/hydroxyl (OH) stoichiometry ratiowas 1.05. The two parts are mixed in a ratio of 1:2, and reacted withthe glass reinforcement (50% fiber volume) with the help of a tincatalyst at a concentration of 0.07%, and cured at 70° C. overnight. Thepolyester groups in Part A impart degradability to the cured matrix, andconsist of caprolactone, lactic acid, and glycolic acid groups. Thecured rods are coated with a 50 micron thick vapor-deposited magnesiumcoating. To increase the adhesion of the barrier to the pins, the pinsare slightly roughened/structured. This rod can then be used for tibiafixation (of femoral fixation, humeral fixation, etc.).

Example 101

This example discusses the splint system with a single pre-cured rod forintramedullary or other bone hole fixation. The diameter of the rod canbe any diameter between 0.5 mm and 20 mm depending on the application.For some applications, the diameter of the rod can be between 1 mm and 7mm. For some other applications, the diameter of the rod can be between6.5 mm and 14 mm. The length of the rod can be between 0.5 cm and 46 cmdepending on the application. For some applications, the length of therod can be between 2 cm and 15 cm. For some other applications, thelength of the rod can be between 12 cm and 30 cm. The rod is placedinside a deflated containment bag. The containment bag is then placedinside the intramedullary (IM) canal of the bone, or inside another bonehole, inflated to the dimensions of the IM canal (e.g., 12.5 mm diameterand 30 cm long) or inflated to the dimensions of another bone hole, andfilled with two-part injectable matrix to occupy the remaining space.The pre-cured rod has the same composition as disclosed in Example 100above, but without a barrier layer. The human implantable degradablecontainment bag is prepared by with multiple co-extruded layers ofpolymers, as discussed in Example 96 above. The calculated water vaportransfer rate (WVTR) of the resulting containment bag is 31 g/m²*day.The two-part injectable matrix consists of Part A and Part B. Part Aconsists of poly(caprolactone-lactic acid) triol (80% by weight),1,4;3,6-dianhydrous-d-sorbitol (15%), and a citric acid ester (5%). PartB is hexamethylene diisocyanate trimer, mixed with 20% biphasic calciumphosphate. Part A and Part B are then injected through a catheter intothe inflated containment bag, and cured under physiological conditions.The resultant curing provides a solid composite implant thatsubstantially conforms to the shape of the IM canal (or other bonehole). Such splint systems can be used for fixation of the tibia,clavicle, humerus, femur, radius, ulna, ribs, etc.

Example 102

This example discusses a splint system with multiple pre-cured pins(rods) for tibial fixation. Multiple pre-cured rods (10-12 in number) ofdiameter 2.2 mm and length of 28 mm are placed inside a deflatedcontainment bag. The containment bag is then placed insideintramedullary (IM) canal of the tibia, inflated to the dimensions ofthe tibial IM canal (e.g., 12.5 mm diameter and 30 cm long), and filledwith two-part injectable matrix to “glue” the pre-cured pins togetherand occupy the remaining space. The pre-cured pins consist of 65%phosphate glass reinforcement braids with remainder being a polymermatrix. The composition of the polymer matrix is similar to thatdisclosed in Example 97 above. The pot life of the two-part injectablematrix after mixing is 3 minutes, and reaches a maximum temperature of45° C. during the cure. Such a composite implant requires a smalleraccess hole (e.g., approximately 2.5-3 mm).

Example 103

This example discusses a splint system with multiple pre-curedreinforcement braids (pins). Multiple reinforcement pins (10-12 innumber) of diameter 2 mm and length of 28 mm are placed inside adeflated containment bag. The containment bag is then placed insideintramedullary (IM) canal of tibia (or other bone), inflated to thedimensions of the tibial IM canal (e.g., 12.5 mm diameter and 30 cmlong), and filled with two-part injectable matrix to “glue” thepre-cured pins and occupy the remaining space. The composition of thepolymer matrix is similar to that disclosed in Example 97 above. The potlife of the two-part injectable matrix after mixing is 3 minutes, andreaches a maximum temperature of 45° C. during the cure. Such an implantrequires a smaller access hole (e.g., approximately 2.25-3 mm).

Example 104

This example describes a process for forming sheets for coatingpre-cured pins and rods. Polycaprolactone (MW of 50,000) was dissolvedin ethyl acetate solvent at a concentration of 25%. Particles of betatricalciumphosphate was then added to the solution at a concentration of5%. The solution was then thoroughly mixed to dissolve thepolycaprolactone (PCL) and efficiently disperse the particles. Sheetswere then drawn out of the solution using a draw-down technique, andthen dried in an oven at 40° C. to remove all the solvent.

Example 105

This example discusses a pre-cured rod (pin). The rod consists of fourelements: glass fibers as reinforcement, sizing on glass fibers, matrix,and a coating. The glass fibers are biodegradable phosphate glass fibersthat release sodium and calcium ions as the fibers degrade. A sizing ofpolyvinylalcohol was applied to the glass fibers for improvedwettability of the polymer matrix. Component A of the polymer matrixconsisted of a poly(caprolactone) triol (70% by weight),1,4;3,6-dianhydrous-d-sorbitol (15%), and a citric acid ester (15%),plus a zirconium catalyst (0.3% by weight). The polyol (component A) wasmixed and crosslinked with a hexamethylene diisocyanate trimer(component B) and 5% beta tricalciumphosphate, to provide a polyurethanematrix that is used in the application to bind reinforcement fibers soas to, ultimately, form a composite implant. The isocyanate(NCO)/hydroxyl (OH) stoichiometry ratio was 1.1. Hydroxyapatite is addedto the polymer matrix as it is biocompatible, osteoinductive, and actsas degradation control buffer. The two parts are reacted with the glassreinforcement (30% fiber volume) with the help of a tin catalyst at aconcentration of 0.07%, and cured at 70° C. overnight. After the rodsare cured, a coating is applied in two stages. In the first stage therods were dip-coated in a solution of 18% polylactic acid and 2%magnesium hydroxide in ethyl acetate. The solvent was allowed tocompletely evaporate by placing them in a 70° C. oven for 1 hour. In thesecond stage, these rods were then coated with a sheet ofpolycaprolactone with beta tricalcium phosphate as disclosed in Example104 above.

Example 106

In this example, a process for making degradable screws is described. Amold, having a cavity which is the shape of a screw, is made by drillingand tapping a Teflon block. Reinforcing glass braid is then insertedthrough the center of the screw-shaped cavity, followed by filling thecavity with a two-part curable polymer matrix as described in Example 97above. The matrix is cured, followed by removal of the screw from themold. An aluminum or stainless steel mold can also be used for improvedfeature resolution. The matrix formulation can, optionally, contain 10%hydroxyapatite particles as an osteoinductive substance.

Example 107

The selection of a catalyst (see Examples 97-106 above) is dependent onmultiple factors, for example, pot life, exotherm properties, mechanicalproperties, as well as potential foaming in case the injectable polymermatrix comes in contact with water.

Max Temp During Cure (Celsius) Pure Polymer With 30% Foaming in CuredMatrix Pot Life Matrix Fiber in Presence of Water Tin 0.05 >30 min 38 27Excessive Foaming 0.09  12 min 57 31 Excessive Foaming 0.13  3.5 min 6848 Excessive Foaming 0.2    <1 min >85  77 Some Foaming Bismuth 0.05 >30min 32 25 Some Foaming 0.09  20 min 54 31 Some Foaming 0.13  4 min 62 44Minimal/No Foaming 0.2   <1 min >85  65 Minimal/No Foaming Zirconium0.05 >30 min 21 21 Does not Cure 0.09 >30 min 21 21 Does not Cure0.13 >30 min 25 22 Some Foaming 0.2   25 min 31 25 Some Foaming 0.3   6min 43 35 Some Foaming

Example 108

Another important criteria is the hydroxyl content in the polyol part(the aforementioned component A) of the formulation. If the hydroxylcontent is too low, the matrix may not cure, or may have lowermechanical properties. On the other hand, if the hydroxyl content ishigh, the implant can heat up significantly due to the heat generatedduring the crosslinking reaction. It is important for the hydroxylcontent to be in the correct range to achieve the desired cure profile,exotherm properties, mechanical properties and Tg of the cured implant.For example, in a particular set of reactions for degradable polyester,the heat of reaction is 1.4 kcal/gram of hydroxyl groups. With hydroxylcontent of 14% in the polyol component, there is a total heat release of200 cal/g of the polyol component, which provides a maximum temperatureof 44° C., and pot life of 4 minutes. However, with a hydroxyl contentof 0.5% in the polyol component, we get a total heat release of 6.8cal/g of the polyol component, which is generally not sufficient to curethe composite implant.

Example 110

As another example of layering materials for a desired goal, abiodegradable polymer, e.g., polycaprolactone (PCL), was wire coatedover glass fibers to form a 2 mm diameter cord. The combination yields auseful cord with stiffness properties that can be used for a variety ofapplications such as parachute cords, fishing nets, etc. The glassfibers, when composed of a soluble glass and exposed to enough water,will change the micro-environment of the fiber and rapidly cause thedegradation of the whole biocomposite leaving environmentally-neutralremains. This could be combined with a rapidly soluble glass andmaterial that degrades by primarily enzymatic mechanisms such as withthe poly-4-hydroxybutyrate (P4HB) above to create a cord thatbiodegrades in an very short time period.

Example 111

Specific to this example, PHAs like P4HB rely on enzymes fordegradation. The ability to encourage nonenzymatic degradation willlikely accelerate the combined rate of degradation and/or allow fordegradation in environments free from biologic activity. Enzymaticdegradation, a consumption process, is initiated from the surfaceinwards and therefore depends on a large surface area-to-mass ratio(such as films) in order to be classified as a biodegradable materialaccording to ISO and ASTM standards. The application of the presentinvention allows simultaneous enzymatic degradation to occur in anoutside-in manner, while the enzyme additive initiates and encouragesdegradation mechanisms within the center of the thicker materials. Thiswill expand the range of materials that can be

classified as biodegradable under ASTM standards, in addition thesolubilized filler (glass fiber) will increase the porosity of thematerial to allow enzymatic degradation throughout the material byincreasing the surface area of the material. As a further expansion ofthis concept, some of the enzyme additives can be produced in a fiberform and used, with appropriate compatibalizers, to increase themechanical properties (e.g., strength and stiffness) of the material,thereby increasing the utility of the material to higher load-bearingapplications while still maintaining a biodegradable classification. Thehigh performance polymers used for engineering applications are highlycross-linked to obtain the mechanical properties desired. Thesematerials are not readily biodegradable in ambient conditions, ifbiodegradable at all in any relevant conditions. The [resent inventionwill allow biodegradable polymers to be used for higher performanceapplications. Currently, biopolymers such as those disclosed above(e.g., PH4B, PLA, etc.) are blended with polysaccharides to increase thedegradation rate. The polysaccharides tend to be sticky and difficult towork with, and have relatively poor mechanical properties. The mechanicsof fiber-loaded composites are well known in the industry.

Example 112

Another example is the stiffening of a polymer with the addition of anadditive (bioglass). In this case, a very low molecular weight polymer,one that can be heated to a low temperature and kneaded by hand withoff-the-shelf bioglass (e.g., silicate-based soluble glass), is used.The bioglass additive was used to significantly increase the stiffnessof the material, in addition, once dissolving, the bioglass will causean internal shift to a basic environment, increasing the degradationrate. Given that the polymer is already at a low molecular weight, thetime it takes to reach a 10,000 cp level for enzymes to complete thedegradation process is much lower and makes this a very rapidlydegrading material.

Example 113

Another example is a flexible composite (e.g., in the form of a rope,cord, sheet, mesh, tube, etc.) fabricated with the reinforcement fibersor braids along with a degradable polymer matrix. These flexiblecomposites (e.g., in the form of a rope, cord, sheet, mesh, tube, etc.)have a bending modulus of preferably less than 5 GPa, preferably lessthan 3 GPa, and more preferably less than 1 GPa. The tensile modulus ofthe ropes, cords, sheets, meshes, tubes, etc. is preferably less than200 GPa, preferably less than 150 GPa, and more preferably less than 100GPa. Also, the tensile modulus of the flexible rope, cord, sheet, mesh,tube, etc. is at least 1 GPa, preferably at least 5 GPa, and morepreferably at least 10 GPa.

MODIFICATIONS OF THE PREFERRED EMBODIMENTS

It should be understood that many additional changes in the details,materials, steps and arrangements of parts, which have been hereindescribed and illustrated in order to explain the nature of the presentinvention, may be made by those skilled in the art while still remainingwithin the principles and scope of the invention.

1.-74. (canceled)
 75. A composite comprising: a layered structure,configured to selectively pass water, the layered structure comprising:a core structure, the core structure comprising: at least onereinforcement element, the at least one reinforcement elementcomprising: a reinforcement element core structure comprising adegradable matrix and at least one filament, wherein the at least onefilament is disposed within the degradable matrix; and an outer regionformed on the reinforcement element core structure, wherein the outerregion of the reinforcement element core structure comprises at leastone layer; and an outer region formed on the core structure, wherein theouter region of the core structure comprises at least one layer.
 76. Acomposite according to claim 75 wherein the degradable matrix comprisesbiodegradable or bioabsorbable materials selected from the groupconsisting of polylactic acid homopolymer or copolymer,polycaprolactone, polyglycolide (PGA), glycolide copolymers,glycolide/lactide copolymers (PGA/PLA), and polylactic acidcocaprolactone block copolymer or random copolymer, polyglycolic acidcopolylactic acid block or random copolymer, stereoisomers andcopolymers of polylactide, poly-L lactide (PLLA), poly-D-lactide (PDLA),poly-DL-lactide (PDLLA), L-lactide, DL-lactide copolymers, L-lactide,D-lactide copolymers, lactide tetramethylene glycolide copolymers,polyhydroxyalkanoate (PHA) homopolymer or copolymer, poly-.beta.hydroxybutyrate (PHB), poly-4-hydroxybutyrate (P4HB), citric acidpolymers, and polyurethanes.
 77. A composite according to claim 75wherein the at least one filament comprises at least one biodegradableor bioabsorbable material selected from the group consisting of silk,resorbable metals, resorbable metal alloys, resorbable ceramics, andphosphate, borate, and silicate soluble glasses.
 78. A compositeaccording to claim 75 wherein the at least one filament comprises asurface coating for improving integration of the at least one filamentwith the degradable matrix.
 79. A composite according to claim 75wherein the reinforcement element core structure comprise a plurality offilaments.
 80. A composite according to claim 79 wherein the pluralityof filaments are disposed substantially parallel to one another.
 81. Acomposite according to claim 79 wherein at least some of the pluralityof filaments are combined so as to form at least one fiber.
 82. Acomposite according to claim 79 wherein at least some of the pluralityof filaments are twisted together so as to form at least one fiber. 83.A composite according to claim 81 wherein the filaments are twisted at arate of up to 2.0 twists per inch.
 84. A composite according to claim 81wherein at least some of the plurality of filaments are twisted togetherso as to form a plurality of fibers.
 85. A composite according to claim81 wherein at least some of the plurality of fibers are disposedsubstantially parallel to one another.
 86. A composite according toclaim 81 wherein at least some of the plurality of fibers are disposedsubstantially transverse to one another.
 87. A composite according toclaim 75 wherein the outer region of the reinforcement element corestructure comprises a degradable polymer.
 88. A composite according toclaim 87 wherein the degradable polymer comprises biodegradable orbioabsorbable materials selected from the group consisting of polylacticacid homopolymer or copolymer, polycaprolactone, polyglycolide (PGA),glycolide copolymers, glycolide/lactide copolymers (PGA/PLA), andpolylactic acid cocaprolactone block copolymer or random copolymer,polyglycolic acid copolylactic acid block or random copolymer,stereoisomers and copolymers of polylactide, poly-L lactide (PLLA),poly-D-lactide (PDLA), poly-DL-lactide (PDLLA), L-lactide, DL-lactidecopolymers, L-lactide, D-lactide copolymers, lactide tetramethyleneglycolide copolymers, polyhydroxyalkanoate (PHA) homopolymer orcopolymer, poly-.beta. hydroxybutyrate (PHB), poly-4-hydroxybutyrate(P4HB), citric acid polymers, and polyurethanes.
 89. A compositeaccording to claim 75 wherein the at least one filament comprisesbetween 5% and 85% by volume of the reinforcement element.
 90. Acomposite according to claim 75 wherein the at least one filamentcomprises between 5% and 65% by volume of the composite.
 91. A compositeaccording to claim 75 wherein the filament volume of the reinforcementelement is greater than the filament volume of the composite.
 92. Acomposite according to claim 75 wherein the core structure comprises aplurality of reinforcement elements embedded in a degradable material.93. A composite according to claim 92 wherein the degradable materialcomprises biodegradable or bioabsorbable materials selected from thegroup consisting of polylactic acid homopolymer or copolymer,polycaprolactone, polyglycolide (PGA), glycolide copolymers,glycolide/lactide copolymers (PGA/PLA), and polylactic acidcocaprolactone block copolymer or random copolymer, polyglycolic acidcopolylactic acid block or random copolymer, stereoisomers andcopolymers of polylactide, poly-L lactide (PLLA), poly-D-lactide (PDLA),poly-DL-lactide (PDLLA), L-lactide, DL-lactide copolymers, L-lactide,D-lactide copolymers, lactide tetramethylene glycolide copolymers,polyhydroxyalkanoate (PHA) homopolymer or copolymer, poly-.beta.hydroxybutyrate (PHB), poly-4-hydroxybutyrate (P4HB), citric acidpolymers, and polyurethanes.
 94. A composite according to claim 92wherein the plurality of reinforcement elements extend substantiallyparallel to one another.
 95. A composite according to claim 92 whereinthe plurality of reinforcement elements extend substantially transverseto one another.
 96. A composite according to claim 92 wherein thefilaments of the plurality of reinforcement elements extendsubstantially parallel to one another.
 97. A composite according toclaim 92 wherein the filaments of the plurality of reinforcementelements extend substantially transverse to one another.
 98. A compositeaccording to claim 75 wherein the outer region formed on the corestructure comprises a degradable composition.
 99. A composite accordingto claim 98 wherein the degradable composition comprises biodegradableor bioabsorbable materials selected from the group consisting ofpolylactic acid homopolymer or copolymer, polycaprolactone,polyglycolide (PGA), glycolide copolymers, glycolide/lactide copolymers(PGA/PLA), and polylactic acid cocaprolactone block copolymer or randomcopolymer, polyglycolic acid copolylactic acid block or randomcopolymer, stereoisomers and copolymers of polylactide, poly-L lactide(PLLA), poly-D-lactide (PDLA), poly-DL-lactide (PDLLA), L-lactide,DL-lactide copolymers, L-lactide, D-lactide copolymers, lactidetetramethylene glycolide copolymers, polyhydroxyalkanoate (PHA)homopolymer or copolymer, poly-.beta. hydroxybutyrate (PHB),poly-4-hydroxybutyrate (P4HB), citric acid polymers, and polyurethanes.100. A composite according to claim 75 wherein the outer region formedon the core structure comprises between 2 and 25 layers.
 101. Acomposite according to claim 100 wherein the layers are characterized byat least one of the group consisting of equal thicknesses and varyingthicknesses.
 102. A composite according to claim 75 wherein the outerregion formed on the core structure comprises an inner layer and anouter layer, wherein the inner layer is thicker than the outer layer.103. A composite according to claim 75 wherein the outer region formedon the core structure is approximately 351 microns thick or less. 104.The composite according to claim 75 wherein the outer region formed onthe core structure provides surface features.
 105. The compositeaccording to claim 104 wherein the surface features comprise at leastone from the group consisting of barbs and threads.
 106. The compositeaccording to claim 75 wherein the outer region formed on the corestructure provides a desired porosity.
 107. A composite according toclaim 75 wherein the outer region comprises a bag.
 108. A compositeaccording to claim 75 wherein the composite comprises one of the groupconsisting of a screw, a rod, a pin, a nail, a bone anchor, bent pin,clip with semielastic properties, and a toggling bone anchor.
 109. Acomposite according to claim 75 wherein a cross-sectional profile of thecomposite comprises one from the group consisting of round, circular,3-sided, 4-sided, 6-sided, 8-sided, cruciform, and multi-lobed.
 110. Amethod for making an anatomical repair, the method comprising: providinga composite comprising: a layered structure, configured to selectivelypass water, the layered structure comprising: a core structure, the corestructure comprising: at least one reinforcement element, the at leastone reinforcement element comprising:   a reinforcement element corestructure comprising a degradable matrix and a plurality of filaments,wherein the plurality of filaments are disposed within the degradablematrix; and   an outer region formed on the reinforcement element corestructure, wherein the outer region of the reinforcement element corestructure comprises at least one layer; and an outer region formed onthe core structure, wherein the outer region of the core structurecomprises at least one layer; and using the composite to repair ananatomical defect.